View source for Oxytocin

{{short description|Peptide hormone and neuropeptide}}
{{About|the hormone|its use as a medication|Oxytocin (medication)|the Billie Eilish song|Oxytocin (song)}}
{{distinguish|Oxycontin}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 691721176
| IUPAC_name = 1-({(4''R'',7''S'',10''S'',13''S'',16''S'',19''R'')-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-16-(4-hydroxybenzyl)-13-[(1''S'')-1-methylpropyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-4-yl}carbonyl)-<small>L</small>-prolyl-<small>L</small>-leucylglycinamide
| image = Oxytocin with labels.png
| image_class = skin-invert-image
| width = 
| image2 = Oxytocin-from-NMR-soln-3D-bs-17.png
| image_class2 = bg-transparent
| ATC_prefix = H01
| ATC_suffix = BB02
| tradename  = Induxin
<!--Physiological data-->
| source_tissues = [[Pituitary gland]]
| target_tissues = Wide spread
| receptors = [[Oxytocin receptor]]
| agonists = 
| antagonists = [[Atosiban]]
| precursor = Oxytocin/neurophysin I prepropeptide
| biosynthesis =

<!--Pharmacokinetic data-->
| pronounce = {{IPAc-en|ˌ|ɒ|k|s|ɪ|ˈ|t|oʊ|s|ɪ|n|audio=LL-Q1860 (eng)-Naomi Persephone Amethyst (NaomiAmethyst)-oxytocin.wav}} {{respell|OK|sih|TOH|sin}}
| bioavailability = 
| protein_bound = 30%
| metabolism = Liver and other [[oxytocinase]]s
| elimination_half-life = 1–6 min (IV)<br />~2 h (intranasal)<ref name="pmid22436536">{{cite journal | vauthors = Weisman O, Zagoory-Sharon O, Feldman R | title = Intranasal oxytocin administration is reflected in human saliva | journal = Psychoneuroendocrinology | volume = 37 | issue = 9 | pages = 1582–1586 | date = September 2012 | pmid = 22436536 | doi = 10.1016/j.psyneuen.2012.02.014 | s2cid = 25253083 }}</ref><ref name="pmid22467107">{{cite journal | vauthors = Huffmeijer R, Alink LR, Tops M, Grewen KM, Light KC, Bakermans-Kranenburg MJ, Ijzendoorn MH | title = Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration | journal = Neuro Endocrinology Letters | volume = 33 | issue = 1 | pages = 21–25 | year = 2012 | pmid = 22467107 }}</ref>
| excretion = Biliary and [[kidney]]

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 50-56-6
| PubChem = 439302
| IUPHAR_ligand = 2174
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00107
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 388434
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 1JQS135EYN
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00089
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 7872
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 395429

<!--Chemical data-->
| C=43 | H=66 | N=12 | O=12 | S=2

| smiles = CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@@H](N)CSSC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C43H66N12O12S2/c1-5-22(4)35-42(66)49-26(12-13-32(45)57)38(62)51-29(17-33(46)58)39(63)53-30(20-69-68-19-25(44)36(60)50-28(40(64)54-35)16-23-8-10-24(56)11-9-23)43(67)55-14-6-7-31(55)41(65)52-27(15-21(2)3)37(61)48-18-34(47)59/h8-11,21-22,25-31,35,56H,5-7,12-20,44H2,1-4H3,(H2,45,57)(H2,46,58)(H2,47,59)(H,48,61)(H,49,66)(H,50,60)(H,51,62)(H,52,65)(H,53,63)(H,54,64)/t22-,25-,26-,27-,28-,29-,30-,31-,35-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XNOPRXBHLZRZKH-DSZYJQQASA-N
}}

<!-- Definition and mechanism -->
'''Oxytocin''' is a [[peptide hormone]] and [[neuropeptide]] normally produced in the [[hypothalamus]] and released by the [[posterior pituitary]].<ref>{{cite book | title = Gray's Anatomy: The Anatomical Basis of Clinical Practice | date = 2015 | publisher = Elsevier Health Sciences | isbn = 978-0-7020-6851-5 | page = 358 | edition = 41 | url = https://books.google.com/books?id=b7FVCgAAQBAJ&pg=PA358 }}</ref> Present in animals since early stages of evolution, in humans it plays roles in behavior that include [[Human bonding|social bonding]], [[love]], [[reproduction]], [[childbirth]], and the [[Postpartum period|period after childbirth]].<ref>{{Cite journal| vauthors = Audunsdottir K, Quintana DS |date=2022-01-25|title=Oxytocin's dynamic role across the lifespan |journal=Aging Brain|volume=2 |language=en|article-number=100028|doi=10.1016/j.nbas.2021.100028|pmid=36908876 |pmc=9997153 |s2cid=246314607|issn=2589-9589|doi-access=free}}</ref><ref>{{cite journal | vauthors = Leng G, Leng RI | title = Oxytocin: A citation network analysis of 10 000 papers | journal = Journal of Neuroendocrinology | volume = 33 | issue = 11 | article-number = e13014 | date = November 2021 | pmid = 34328668 | doi = 10.1111/jne.13014 | s2cid = 236516186 | doi-access = free | hdl = 20.500.11820/d2bdf31e-1d12-4abf-80a3-659a7e31a9f7 | hdl-access = free }}</ref><ref name="pmid12000539">{{cite journal | vauthors = Francis DD, Young LJ, Meaney MJ, Insel TR | title = Naturally occurring differences in maternal care are associated with the expression of oxytocin and vasopressin (V1a) receptors: gender differences | journal = Journal of Neuroendocrinology | volume = 14 | issue = 5 | pages = 349–53 | date = May 2002 | pmid = 12000539 | doi = 10.1046/j.0007-1331.2002.00776.x | s2cid = 16005801 }}</ref><ref name="pmid11573971">{{cite journal | vauthors = Gainer H, Fields RL, House SB | title = Vasopressin gene expression: experimental models and strategies | journal = Experimental Neurology | volume = 171 | issue = 2 | pages = 190–9 | date = October 2001 | pmid = 11573971 | doi = 10.1006/exnr.2001.7769 | s2cid = 25718623 }}</ref> Oxytocin is released into the bloodstream as a hormone in response to [[Human sexual activity|sexual activity]] and during childbirth.<ref name=Rogers>{{cite web | vauthors = Rogers K |title=Oxytocin |url=https://www.britannica.com/science/oxytocin |website=Encyclopædia Britannica |date=7 July 2023 }}</ref><ref name=Chi2012>{{cite book | vauthors = Chiras DD | title = Human Biology | date = 2012 | publisher = Jones & Bartlett Learning | location = Sudbury, MA | isbn = 978-0-7637-8345-7 | page = 262 | edition = 7th | url = https://books.google.com/books?id=mqlY1n8Ez1oC&pg=PA262 }}</ref> It is also available in [[Oxytocin (medication)|pharmaceutical form]]. In either form, oxytocin stimulates uterine contractions to speed up the process of childbirth.

In its natural form, it also plays a role in [[maternal bonding]] and [[lactation|milk production]].<ref name="Chi2012" /><ref>{{cite book | title = Human Evolutionary Biology | date = 2010 | publisher = Cambridge University Press | isbn = 978-1-139-78900-4 | page = 282 | url = https://books.google.com/books?id=3NRf_8gwmO8C&pg=PA282 }}</ref> Production and secretion of oxytocin is controlled by a [[positive feedback]] mechanism, where its initial release stimulates production and release of further oxytocin. For example, when oxytocin is released during a contraction of the uterus at the start of childbirth, this stimulates production and release of more oxytocin and an increase in the intensity and frequency of contractions. This process compounds in intensity and frequency and continues until the triggering activity ceases. A similar process takes place during lactation and during sexual activity.

Oxytocin is derived by [[enzymatic]] splitting from the [[peptide precursor]] encoded by the human OXT [[gene]]. The deduced structure of the active nonapeptide is:

{{block indent| [[cysteine|Cys]]&nbsp;–&nbsp;[[tyrosine|Tyr]]&nbsp;–&nbsp;[[isoleucine|Ile]]&nbsp;–&nbsp;[[glutamine|Gln]]&nbsp;–&nbsp;[[asparagine|Asn]]&nbsp;–&nbsp;Cys&nbsp;–&nbsp;[[proline|Pro]]&nbsp;–&nbsp;[[leucine|Leu]]&nbsp;–&nbsp;[[glycine|Gly]]&nbsp;–&nbsp;NH<sub>2</sub>, or CYIQNCPLG-NH<sub>2</sub>.{{Citation needed|date=September 2025}}}}

== Etymology ==
The term "oxytocin" derives from the Greek {{lang|grc|[[wikt:ὀξυτόκιον|ὀξυτόκιον]]}} ({{lang|grc-Latn|oxytokion}}), based on {{lang|grc|[[wikt:ὀξύς|ὀξύς]]}} ({{lang|grc-Latn|oxús}}), meaning "sharp" or "swift", and {{lang|grc|[[wikt:τόκος|τόκος]]}} ({{lang|grc-Latn|tókos}}), meaning "childbirth".<ref>{{Cite dictionary |title=oxytocic |dictionary=Wiktionary|url=https://en.wiktionary.org/wiki/oxytocic|access-date=2021-08-05|date=14 October 2019|language=en}}</ref><ref>{{Cite dictionary |title=oxytocin |dictionary=Wiktionary|url=https://en.wiktionary.org/wiki/oxytocin|access-date=2021-08-05|date=15 July 2021|language=en}}</ref>{{user-generated inline|date=August 2025}} The adjective form is "oxytocic", which refers to medicines which stimulate uterine contractions, to speed up the process of childbirth. Colloquially, it has been referred to as the "cuddle hormone," "hug hormone" or the "love hormone" because of extensive evidence of its involvement in mating and social behavior. It has been shown to be involved in mating behavior in animals as low as C. elegans.

== History ==
The uterine-contracting properties of the principle that would later be named oxytocin were discovered by British pharmacologist [[Henry Hallett Dale]] in 1906,<ref name= "pmid16992821">{{cite journal | vauthors = Dale HH | title = On some physiological actions of ergot | journal = The Journal of Physiology | volume = 34 | issue = 3 | pages = 163–206 | date = May 1906 | pmid = 16992821 | pmc = 1465771 | doi = 10.1113/jphysiol.1906.sp001148 }}</ref><ref name="pmid19482229"/> and its milk ejection property was described by Ott and Scott in 1910<ref>{{cite journal | doi = 10.3181/00379727-8-27 | title = The action of infundibulin upon the mammary secretion |journal=Experimental Biology and Medicine |volume=8 |issue=2 |pages=48–49 |year=1910 | vauthors = Ott I, Scott JC | s2cid = 87519246 |url=https://zenodo.org/record/1450228 }}</ref> and by Schafer and Mackenzie in 1911.<ref name=Schafer_Mackenzie_1911>{{cite journal | vauthors = Schafer EA, Mackenzie K | title = The Action of Animal Extracts on Milk Secretion |journal = Proceedings of the Royal Society B |date=July 1911 | volume = 84 | issue = 568 |pages = 16–22 | doi = 10.1098/rspb.1911.0042 | bibcode = 1911RSPSB..84...16S | doi-access = free }}</ref> In 1909 the first clinical use of oxytocin was performed by  [[William Blair-Bell]] to induce childbirth in patients with complications.<ref>{{cite journal | vauthors = Bell WB | title = The Pituitary Body and the Therapeutic Value of the Infundibular Extract in Shock, Uterine Atony, and Intestinal Paresis | journal = British Medical Journal | volume = 2 | issue = 2553 | pages = 1609–1613 | date = December 1909 | pmid = 20764780 | pmc = 2321437 | doi = 10.1136/bmj.2.2553.1609 }}</ref><ref>{{cite journal | vauthors = Stone ML | title = The intravenous use of dilute pituitrin for the induction and stimulation of labor | journal = American Journal of Obstetrics and Gynecology | volume = 59 | issue = 1 | pages = 49–57 | date = January 1950 | pmid = 15399625 | doi = 10.1016/0002-9378(50)90340-1 }}</ref>

By the 1920s, oxytocin and [[vasopressin]] had been isolated from [[Pituitary gland|pituitary]] tissue and given their current names. Oxytocin's molecular structure was determined in 1952.<ref>{{cite book | vauthors = Corey EJ | title = Molecules and Medicine | date = 2012 | publisher = John Wiley & Sons | isbn = 978-1-118-36173-3 | chapter-url = https://books.google.com/books?id=jz2GN6DYoOoC&pg=RA1-PT110 | chapter = Oxytocin }}</ref> In the early 1950s, American biochemist [[Vincent du Vigneaud]] found that oxytocin is made up of nine [[amino acid]]s, and he identified its amino acid sequence, the first [[Peptide|polypeptide]] hormone to be sequenced.<ref name="pmid13129273">{{cite journal | vauthors = Du Vigneaud V, Ressler C, Trippett S | title = The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin | journal = The Journal of Biological Chemistry | volume = 205 | issue = 2 | pages = 949–957 | date = December 1953 | pmid = 13129273 | doi = 10.1016/S0021-9258(18)49238-1 | doi-access = free }}</ref> In 1953, du Vigneaud carried out the synthesis of oxytocin, the first polypeptide [[hormone]] to be synthesized.<ref>{{cite journal | vauthors = Lee HJ, Macbeth AH, Pagani JH, Young WS | title = Oxytocin: the great facilitator of life | journal = Progress in Neurobiology | volume = 88 | issue = 2 | pages = 127–151 | date = June 2009 | pmid = 19482229 | pmc = 2689929 | doi = 10.1016/j.pneurobio.2009.04.001 | publisher = US National Library of Medicine National Institutes of Health }}</ref><ref>{{Cite journal|vauthors=du Vigneaud V, Ressler C, Swan JM, Roberts CW, Katsoyannis PG, Gordon S | title = The synthesis of an octapeptide amide with the hormonal activity of oxytocin | journal = J. Am. Chem. Soc. | volume = 75 | issue = 19 | pages = 4879–80 | year = 1953 | doi = 10.1021/ja01115a553 | bibcode = 1953JAChS..75.4879V }}</ref><ref name="du_Vigneaud_1954">{{cite journal | vauthors = du Vigneaud V, Ressler C, Swan JM, Roberts CW, Katsoyannis PG | journal = Journal of the American Chemical Society | year = 1954 | volume = 76 | issue = 12 | pages = 3115–21 | doi = 10.1021/ja01641a004 | title = The Synthesis of Oxytocin1| bibcode = 1954JAChS..76.3115D }}</ref> Du Vigneaud was awarded the [[Nobel Prize in Chemistry]] in 1955 for his work.<ref name="pmid13324123">{{cite journal | vauthors = Du Vigneaud V | title = Trail of sulfur research: from insulin to oxytocin | journal = Science | volume = 123 | issue = 3205 | pages = 967–974 | date = June 1956 | pmid = 13324123 | doi = 10.1126/science.123.3205.967 | bibcode = 1956Sci...123..967D }}</ref> Further work on different synthetic routes for oxytocin, as well as the preparation of analogues of the hormone (''e.g.'' 4-deamido-oxytocin) was performed in the following decade by [[Iphigenia Photaki]].<ref name=":2">{{Cite book|url=http://jupiter.chem.uoa.gr/thanost/fotaki/Fotaki_cv_1968.pdf|title=Iphigenia Vourvidou-Photaki: Biographical Statement and Scientific Work|publisher=F. Konstantinidis & K. Mihalas|year=1968|location=Athens|pages=5–42|language=el|access-date=2021-04-13|archive-date=2021-04-12|archive-url=https://web.archive.org/web/20210412220140/http://jupiter.chem.uoa.gr/thanost/fotaki/Fotaki_cv_1968.pdf}}</ref>

==Biochemistry==
{{#invoke:Infobox_gene|getTemplateData|QID=Q14820911|entity_mouse=Q14820914}}

[[Estrogen]] has been found to increase the [[secretion]] of oxytocin and to increase the [[gene expression|expression]] of its [[receptor (biochemistry)|receptor]], the [[oxytocin receptor]], in the brain.<ref name="GoldsteinMeston2005">{{cite book | vauthors = Goldstein I, Meston CM, Davis S, Traish A | title = Women's Sexual Function and Dysfunction: Study, Diagnosis and Treatment|url=https://books.google.com/books?id=3J7TnwpbZQwC&pg=PA205|date=17 November 2005|publisher=CRC Press|isbn=978-1-84214-263-9|pages=205–}}</ref> In women, a single dose of [[estradiol]] has been found to be sufficient to increase circulating oxytocin concentrations.<ref name="Acevedo-RodriguezMani2015" />

===Biosynthesis===
Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides, including [[corticotropin-releasing hormone]] and [[dynorphin]], for example, that act locally. The magnocellular [[neuron]]s that make oxytocin are adjacent to magnocellular neurons that make vasopressin and are similar in many respects.

[[File:The biosynthesis of the different forms of OT.jpg|class=skin-invert-image|alt=The biosynthesis of the different forms of OT|left|thumb|The biosynthesis of the different forms of OT]]

The oxytocin peptide is synthesized as an inactive precursor protein from the ''OXT'' [[gene]].<ref name="pmid2991279">{{cite journal | vauthors = Sausville E, Carney D, Battey J | title = The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line | journal = The Journal of Biological Chemistry | volume = 260 | issue = 18 | pages = 10236–10241 | date = August 1985 | pmid = 2991279 | doi = 10.1016/S0021-9258(17)39236-0 | doi-access = free }}</ref><ref name="pmid1968469">{{cite journal | vauthors = Repaske DR, Phillips JA, Kirby LT, Tze WJ, D'Ercole AJ, Battey J | title = Molecular analysis of autosomal dominant neurohypophyseal diabetes insipidus | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 70 | issue = 3 | pages = 752–757 | date = March 1990 | pmid = 1968469 | doi = 10.1210/jcem-70-3-752 }}</ref><ref name="pmid1978246">{{cite journal | vauthors = Summar ML, Phillips JA, Battey J, Castiglione CM, Kidd KK, Maness KJ, Weiffenbach B, Gravius TC | title = Linkage relationships of human arginine vasopressin-neurophysin-II and oxytocin-neurophysin-I to prodynorphin and other loci on chromosome 20 | journal = Molecular Endocrinology | volume = 4 | issue = 6 | pages = 947–950 | date = June 1990 | pmid = 1978246 | doi = 10.1210/mend-4-6-947 | doi-access = free }}</ref> This precursor protein also includes the oxytocin carrier protein [[neurophysin I]].<ref name="pmid6153132">{{cite journal | vauthors = Brownstein MJ, Russell JT, Gainer H | title = Synthesis, transport, and release of posterior pituitary hormones | journal = Science | volume = 207 | issue = 4429 | pages = 373–378 | date = January 1980 | pmid = 6153132 | doi = 10.1126/science.6153132 | bibcode = 1980Sci...207..373B }}</ref> The inactive precursor protein is progressively [[Hydrolysis|hydrolyzed]] into smaller fragments (one of which is neurophysin I) via a series of enzymes. The last hydrolysis that releases the active oxytocin nonapeptide is catalyzed by [[peptidylglycine alpha-amidating monooxygenase]] (PAM).<ref name="pmid2769155">{{cite journal | vauthors = Sheldrick EL, Flint AP | title = Post-translational processing of oxytocin-neurophysin prohormone in the ovine corpus luteum: activity of peptidyl glycine alpha-amidating mono-oxygenase and concentrations of its cofactor, ascorbic acid | journal = The Journal of Endocrinology | volume = 122 | issue = 1 | pages = 313–322 | date = July 1989 | pmid = 2769155 | doi = 10.1677/joe.0.1220313 }}</ref>

The activity of the PAM enzyme system is dependent upon [[vitamin C]] (ascorbate), which is a necessary vitamin cofactor. By chance, sodium ascorbate by itself was found to stimulate the production of oxytocin from ovarian tissue over a range of concentrations in a dose-dependent manner.<ref name="pmid3668432">{{cite journal | vauthors = Luck MR, Jungclas B | title = Catecholamines and ascorbic acid as stimulators of bovine ovarian oxytocin secretion | journal = The Journal of Endocrinology | volume = 114 | issue = 3 | pages = 423–430 | date = September 1987 | pmid = 3668432 | doi = 10.1677/joe.0.1140423 | url = http://pdfs.semanticscholar.org/33e5/c9763f61a7d64b0bc266e06461f4d3fb845a.pdf | s2cid = 24630906 | archive-url = https://web.archive.org/web/20190222084609/http://pdfs.semanticscholar.org/33e5/c9763f61a7d64b0bc266e06461f4d3fb845a.pdf | archive-date = 2019-02-22 }}</ref> Many of the same tissues (''e.g.'' ovaries, testes, eyes, adrenals, placenta, thymus, pancreas) where PAM (and oxytocin by default) is found are also known to store higher concentrations of vitamin C.<ref name="pmid1106295">{{cite journal | vauthors = Hornig D | title = Distribution of ascorbic acid, metabolites and analogues in man and animals | journal = Annals of the New York Academy of Sciences | volume = 258 | issue = 1 | pages = 103–118 | date = September 1975 | pmid = 1106295 | doi = 10.1111/j.1749-6632.1975.tb29271.x | s2cid = 22881895 | bibcode = 1975NYASA.258..103H }}</ref>

Oxytocin is known to be metabolized by the [[oxytocinase]], [[leucyl/cystinyl aminopeptidase]].<ref name="pmid16054015">{{cite journal | vauthors = Tsujimoto M, Hattori A | title = The oxytocinase subfamily of M1 aminopeptidases | journal = Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics | volume = 1751 | issue = 1 | pages = 9–18 | date = August 2005 | pmid = 16054015 | doi = 10.1016/j.bbapap.2004.09.011 }}</ref><ref name="pmid15894523">{{cite journal | vauthors = Nomura S, Ito T, Yamamoto E, Sumigama S, Iwase A, Okada M, Shibata K, Ando H, Ino K, Kikkawa F, Mizutani S | title = Gene regulation and physiological function of placental leucine aminopeptidase/oxytocinase during pregnancy | journal = Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics | volume = 1751 | issue = 1 | pages = 19–25 | date = August 2005 | pmid = 15894523 | doi = 10.1016/j.bbapap.2005.04.006 }}</ref> Other oxytocinases are also known to exist.<ref name="pmid16054015" /><ref name="pmid1355623">{{cite journal | vauthors = Mizutani S, Yokosawa H, Tomoda Y | title = Degradation of oxytocin by the human placenta: effect of selective inhibitors | journal = Acta Endocrinologica | volume = 127 | issue = 1 | pages = 76–80 | date = July 1992 | pmid = 1355623 | doi = 10.1530/acta.0.1270076 | url = http://pdfs.semanticscholar.org/5089/5066bc37420c42af58e4d4849bdb04f2bd2f.pdf | s2cid = 21289122 | archive-url = https://web.archive.org/web/20190224042557/http://pdfs.semanticscholar.org/5089/5066bc37420c42af58e4d4849bdb04f2bd2f.pdf | archive-date = 2019-02-24 }}</ref> [[Amastatin]], [[bestatin]] (ubenimex), [[leupeptin]], and [[puromycin]] have been found to inhibit the enzymatic degradation of oxytocin, though they also inhibit the degradation of various other peptides, such as [[vasopressin]], [[met-enkephalin]], and [[dynorphin A]].<ref name="pmid1355623" /><ref name="pmid6540873">{{cite journal | vauthors = Meisenberg G, Simmons WH | title = Amastatin potentiates the behavioral effects of vasopressin and oxytocin in mice | journal = Peptides | volume = 5 | issue = 3 | pages = 535–539 | year = 1984 | pmid = 6540873 | doi = 10.1016/0196-9781(84)90083-4 | s2cid = 3881661 | title-link = vasopressin }}</ref><ref name="pmid1800950">{{cite journal | vauthors = Stancampiano R, Melis MR, Argiolas A | title = Proteolytic conversion of oxytocin by brain synaptic membranes: role of aminopeptidases and endopeptidases | journal = Peptides | volume = 12 | issue = 5 | pages = 1119–1125 | year = 1991 | pmid = 1800950 | doi = 10.1016/0196-9781(91)90068-z | s2cid = 36706540 }}</ref><ref name="pmid9013800">{{cite journal | vauthors = Itoh C, Watanabe M, Nagamatsu A, Soeda S, Kawarabayashi T, Shimeno H | title = Two molecular species of oxytocinase (L-cystine aminopeptidase) in human placenta: purification and characterization | journal = Biological & Pharmaceutical Bulletin | volume = 20 | issue = 1 | pages = 20–24 | date = January 1997 | pmid = 9013800 | doi = 10.1248/bpb.20.20 | doi-access = free }}</ref>

===Neural sources===
In the [[hypothalamus]], oxytocin is made in [[magnocellular neurosecretory cell]]s of the [[supraoptic nucleus|supraoptic]] and [[Paraventricular nucleus of hypothalamus|paraventricular nuclei]],<ref name="Sukhov 1993">{{cite journal | vauthors = Sukhov RR, Walker LC, Rance NE, Price DL, Young WS | title = Vasopressin and oxytocin gene expression in the human hypothalamus | journal = The Journal of Comparative Neurology | volume = 337 | issue = 2 | pages = 295–306 | date = November 1993 | pmid = 8277003 | doi = 10.1002/cne.903370210 | pmc = 9883978 | s2cid = 35174328 }}</ref> and is stored in [[Herring bodies]] at the [[axon]] terminals in the posterior pituitary. It is then released into the blood from the [[posterior pituitary|posterior lobe]] (neurohypophysis) of the [[pituitary gland]]. These axons (likely, but [[dendrites]] have not been ruled out) have collaterals that innervate neurons in the [[nucleus accumbens]], a brain structure where oxytocin receptors are expressed.<ref name="Ross">{{cite journal | vauthors = Ross HE, Cole CD, Smith Y, Neumann ID, Landgraf R, Murphy AZ, Young LJ | title = Characterization of the oxytocin system regulating affiliative behavior in female prairie voles | journal = Neuroscience | volume = 162 | issue = 4 | pages = 892–903 | date = September 2009 | pmid = 19482070 | pmc = 2744157 | doi = 10.1016/j.neuroscience.2009.05.055 }}</ref> The [[endocrine system|endocrine]] effects of hormonal oxytocin, and the cognitive or behavioral effects of oxytocin [[neuropeptide]]s are thought to be coordinated through its common release through these collaterals.<ref name="Ross"/> Oxytocin is also produced by some neurons in the paraventricular nucleus that project to other parts of the brain and to the spinal cord.<ref>{{cite journal | vauthors = Landgraf R, Neumann ID | title = Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication | journal = Frontiers in Neuroendocrinology | volume = 25 | issue = 3–4 | pages = 150–176 | year = 2004 | pmid = 15589267 | doi = 10.1016/j.yfrne.2004.05.001 | s2cid = 30507377 }}</ref> Depending on the species, oxytocin receptor-expressing cells are located in other areas, including the [[amygdala]] and [[Stria terminalis#Bed nucleus of the stria terminalis|bed nucleus of the stria terminalis]].

In the pituitary gland, oxytocin is packaged in large, dense-core vesicles, where it is bound to [[neurophysin I]] as shown in the inset of the figure; neurophysin is a large peptide fragment of the larger precursor [[protein]] molecule from which oxytocin is derived by [[enzyme|enzymatic]] cleavage.

Secretion of oxytocin from the neurosecretory nerve endings is regulated by the electrical activity of the oxytocin cells in the hypothalamus. These cells generate [[action potential]]s that propagate down axons to the nerve endings in the pituitary; the endings contain large numbers of oxytocin-containing vesicles, which are released by [[exocytosis]] when the nerve terminals are depolarised.

===Non-neural sources===
Endogenous oxytocin concentrations in the brain have been found to be as much as 1000-fold higher than peripheral levels.<ref name="BaribeauAnagnostou2015">{{cite journal | vauthors = Baribeau DA, Anagnostou E | title = Oxytocin and vasopressin: linking pituitary neuropeptides and their receptors to social neurocircuits | journal = Frontiers in Neuroscience | volume = 9 | page = 335 | year = 2015 | pmid = 26441508 | pmc = 4585313 | doi = 10.3389/fnins.2015.00335 | doi-access = free }}</ref> Outside the brain, oxytocin-containing cells have been identified in several diverse tissues, including in females in the [[corpus luteum]]<ref name="pmid7078636">{{cite journal | vauthors = Wathes DC, Swann RW | title = Is oxytocin an ovarian hormone? | journal = Nature | volume = 297 | issue = 5863 | pages = 225–227 | date = May 1982 | pmid = 7078636 | doi = 10.1038/297225a0 | s2cid = 4364778 | bibcode = 1982Natur.297..225W }}</ref><ref name="pmid6124806">{{cite journal | vauthors = Wathes DC, Swann RW, Pickering BT, Porter DG, Hull MG, Drife JO | title = Neurohypophysial hormones in the human ovary | journal = Lancet | volume = 2 | issue = 8295 | pages = 410–412 | date = August 1982 | pmid = 6124806 | doi = 10.1016/S0140-6736(82)90441-X | s2cid = 42282964 }}</ref> and the [[placenta]];<ref name="pmid6832059">{{cite journal | vauthors = Fields PA, Eldridge RK, Fuchs AR, Roberts RF, Fields MJ | title = Human placental and bovine corpora luteal oxytocin | journal = Endocrinology | volume = 112 | issue = 4 | pages = 1544–1546 | date = April 1983 | pmid = 6832059 | doi = 10.1210/endo-112-4-1544 }}</ref> in males in the testicles' [[Leydig cell|interstitial cells of Leydig]];<ref name="pmid3995564">{{cite journal | vauthors = Guldenaar SE, Pickering BT | title = Immunocytochemical evidence for the presence of oxytocin in rat testis | journal = Cell and Tissue Research | volume = 240 | issue = 2 | pages = 485–487 | year = 1985 | pmid = 3995564 | doi = 10.1007/BF00222364 | s2cid = 34325145 }}</ref> and in both sexes in the [[retina]],<ref name="pmid6647119">{{cite journal | vauthors = Gauquelin G, Geelen G, Louis F, Allevard AM, Meunier C, Cuisinaud G, Benjanet S, Seidah NG, Chretien M, Legros JJ | title = Presence of vasopressin, oxytocin and neurophysin in the retina of mammals, effect of light and darkness, comparison with the neuropeptide content of the neurohypophysis and the pineal gland | journal = Peptides | volume = 4 | issue = 4 | pages = 509–515 | year = 1983 | pmid = 6647119 | doi = 10.1016/0196-9781(83)90056-6 | s2cid = 3848055 }}</ref> the [[adrenal medulla]],<ref name="pmid6699132">{{cite journal | vauthors = Ang VT, Jenkins JS | title = Neurohypophysial hormones in the adrenal medulla | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 58 | issue = 4 | pages = 688–691 | date = April 1984 | pmid = 6699132 | doi = 10.1210/jcem-58-4-688 }}</ref> the [[thymus]]<ref name="pmid3961493">{{cite journal | vauthors = Geenen V, Legros JJ, Franchimont P, Baudrihaye M, Defresne MP, Boniver J | title = The neuroendocrine thymus: coexistence of oxytocin and neurophysin in the human thymus | journal = Science | volume = 232 | issue = 4749 | pages = 508–511 | date = April 1986 | pmid = 3961493 | doi = 10.1126/science.3961493 | bibcode = 1986Sci...232..508G | hdl = 2268/16909 | url = http://orbi.ulg.ac.be/handle/2268/16909 | hdl-access = free }}</ref> and the [[pancreas]].<ref name="pmid3195625">{{cite journal | vauthors = Amico JA, Finn FM, Haldar J | title = Oxytocin and vasopressin are present in human and rat pancreas | journal = The American Journal of the Medical Sciences | volume = 296 | issue = 5 | pages = 303–307 | date = November 1988 | pmid = 3195625 | doi = 10.1097/00000441-198811000-00003 | s2cid = 20084873 }}</ref> The finding of significant amounts of this classically "[[neurohypophysial hormone|neurohypophysial]]" hormone outside the central nervous system raises many questions regarding its possible importance in these diverse tissues.

The [[Leydig cells]] in some species have been shown to possess the biosynthetic machinery to manufacture testicular oxytocin ''de novo'', to be specific, in rats (which can synthesize vitamin C endogenously), and in guinea pigs, which, like humans, require an [[Exogeny|exogenous]] source of vitamin C in their diets.<ref name="pmid1456839">{{cite journal | vauthors = Kukucka MA, Misra HP | title = HPLC determination of an oxytocin-like peptide produced by isolated guinea pig Leydig cells: stimulation by ascorbate | journal = Archives of Andrology | volume = 29 | issue = 2 | pages = 185–190 | year = 1992 | pmid = 1456839 | doi = 10.3109/01485019208987723 | doi-access = free }}</ref> Oxytocin is synthesized by [[corpora lutea]] of several species, including ruminants and primates. Along with [[estrogen]], it is involved in inducing the endometrial synthesis of [[prostaglandin F2alpha|prostaglandin&nbsp;F<sub>2α</sub>]] to cause regression of the [[corpus luteum]].<ref>[http://www.journalofdairyscience.org/article/S0739-7240(02)00161-3/fulltext] {{dead link|date=November 2021}}</ref>

===Evolution===
Virtually all [[vertebrate]]s have an oxytocin-like [[nonapeptide]] hormone that supports reproductive functions and a vasopressin-like nonapeptide hormone involved in water regulation. The two genes are usually located close to each other (less than 15,000 bases apart) on the same [[chromosome]], and are transcribed in opposite directions (however, in [[fugu]],<ref name="pmid9356472">{{cite journal | vauthors = Venkatesh B, Si-Hoe SL, Murphy D, Brenner S | title = Transgenic rats reveal functional conservation of regulatory controls between the Fugu isotocin and rat oxytocin genes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 23 | pages = 12462–12466 | date = November 1997 | pmid = 9356472 | pmc = 25001 | doi = 10.1073/pnas.94.23.12462 | doi-access = free | bibcode = 1997PNAS...9412462V }}</ref> the homologs are further apart and transcribed in the same direction). The two genes are believed to result from a [[gene duplication]] event; the ancestral gene is estimated to be about 500 million years old and is found in [[cyclostomata]] (modern members of the [[Agnatha]]).<ref name=":0">{{cite journal | vauthors = Gimpl G, Fahrenholz F | title = The oxytocin receptor system: structure, function, and regulation | journal = Physiological Reviews | volume = 81 | issue = 2 | pages = 629–683 | date = April 2001 | pmid = 11274341 | doi = 10.1152/physrev.2001.81.2.629 | url = http://pdfs.semanticscholar.org/14c0/e893e3b4453c46c0466efdf7fde471318935.pdf | s2cid = 13265083 | archive-url = https://web.archive.org/web/20201116073733/http://pdfs.semanticscholar.org/14c0/e893e3b4453c46c0466efdf7fde471318935.pdf | archive-date = 2020-11-16 }}</ref>

A 2023 study found that [[zebrafish]] utilize oxytocin in reaction to the fear of other fish. It found that zebrafish that have had oxytocin production removed by [[Genetic engineering|gene editing]] cannot respond to the fear of other fish. When oxytocin is injected back into the fish, they react again in a way that suggests they may have empathy in regards to this emotion. Furthermore, because the same regions of the brain are involved as in mammals, the study suggests oxytocin-based empathy may have evolved from a common ancestor many millions of years ago.<ref>{{cite journal | vauthors = Akinrinade I, Kareklas K, Teles MC, Reis TK, Gliksberg M, Petri G, Levkowitz G, Oliveira RF | title = Evolutionarily conserved role of oxytocin in social fear contagion in zebrafish | journal = Science | volume = 379 | issue = 6638 | pages = 1232–1237 | date = March 2023 | pmid = 36952426 | doi = 10.1126/science.abq5158 | bibcode = 2023Sci...379.1232A }}</ref>

==Biological function==
Oxytocin has peripheral (hormonal) actions and also has actions in the brain. Its actions are mediated by specific [[oxytocin receptor]]s. The oxytocin receptor is a [[G-protein-coupled receptor]], OT-R, which requires [[magnesium]] and [[cholesterol]] and is expressed in [[Myometrium|myometrial cells]].<ref>{{cite journal | vauthors = Quattropani A, Dorbais J, Covini D, Pittet PA, Colovray V, Thomas RJ, Coxhead R, Halazy S, Scheer A, Missotten M, Ayala G, Bradshaw C, De Raemy-Schenk AM, Nichols A, Cirillo R, Tos EG, Giachetti C, Golzio L, Marinelli P, Church DJ, Barberis C, Chollet A, Schwarz MK | title = Discovery and development of a new class of potent, selective, orally active oxytocin receptor antagonists | journal = Journal of Medicinal Chemistry | volume = 48 | issue = 24 | pages = 7882–7905 | date = December 2005 | pmid = 16302826 | doi = 10.1021/jm050645f | s2cid = 11213732 }}</ref> It belongs to the [[Rhodopsin-like receptors|rhodopsin-type]] (class I) group of G-protein-coupled receptors.<ref name=":0"/>

Studies have looked at oxytocin's role in various behaviors, including [[orgasm]], [[social recognition]], [[pair bond]]ing, [[anxiety]], in-group [[bias]], situational lack of [[honesty]], [[autism]], and maternal behaviors.<ref name="pmid19482229">{{cite journal | vauthors = Lee HJ, Macbeth AH, Pagani JH, Young WS | title = Oxytocin: the great facilitator of life | journal = Progress in Neurobiology | volume = 88 | issue = 2 | pages = 127–151 | date = June 2009 | pmid = 19482229 | pmc = 2689929 | doi = 10.1016/j.pneurobio.2009.04.001 }}</ref> Oxytocin is believed to have a significant role in social learning. There are indicators that oxytocin may help to decrease noise in the brain's auditory system, increase perception of social cues and support more targeted social behavior. It may also enhance reward responses. However, its effects may be influenced by context, such as the presence of familiar or unfamiliar individuals.<ref name="Holmes">{{cite journal | vauthors = Holmes B |title=Oxytocin's effects aren't just about love |journal=Knowable Magazine |date=11 February 2022 |doi=10.1146/knowable-021122-1 |url=https://knowablemagazine.org/article/mind/2022/oxytocins-effects-arent-just-about-love |doi-access=free |access-date=15 February 2022|url-access=subscription }}</ref><ref name="Froemke">{{cite journal | vauthors = Froemke RC, Young LJ | title = Oxytocin, Neural Plasticity, and Social Behavior | journal = Annual Review of Neuroscience | volume = 44 | issue = 1 | pages = 359–381 | date = July 2021 | pmid = 33823654 | doi = 10.1146/annurev-neuro-102320-102847 | pmc = 8604207 }}</ref> In addition to its oxytocin receptor agonism, oxytocin has been found to act as a PAM of the [[μ-opioid receptor|μ-]] and [[κ-opioid receptor]]s and this may be involved in its [[analgesic]] effects.<ref name="DrakopoulosMoianosPrifti2022">{{cite journal | vauthors = Drakopoulos A, Moianos D, Prifti GM, Zoidis G, Decker M | title = Opioid Ligands Addressing Unconventional Binding Sites and More Than One Opioid Receptor Subtype | journal = ChemMedChem | volume = 17 | issue = 14 | article-number = e202200169 | date = July 2022 | pmid = 35560796 | doi = 10.1002/cmdc.202200169 | url = }}</ref><ref name="KaczyńskaWojciechowski2021">{{cite journal | vauthors = Kaczyńska K, Wojciechowski P | title = Non-Opioid Peptides Targeting Opioid Effects | journal = Int J Mol Sci | volume = 22 | issue = 24 | date = December 2021 | article-number = 13619 | pmid = 34948415 | pmc = 8709238 | doi = 10.3390/ijms222413619 | doi-access = free | url = }}</ref><ref name="CarterKingsbury2022">{{cite journal | vauthors = Carter CS, Kingsbury MA | title = Oxytocin and oxygen: the evolution of a solution to the 'stress of life' | journal = Philos Trans R Soc Lond B Biol Sci | volume = 377 | issue = 1858 | article-number = 20210054 | date = August 2022 | pmid = 35856299 | pmc = 9272143 | doi = 10.1098/rstb.2021.0054 | url = }}</ref><ref name="MeguroMiyanoHirayama2018">{{cite journal | vauthors = Meguro Y, Miyano K, Hirayama S, Yoshida Y, Ishibashi N, Ogino T, Fujii Y, Manabe S, Eto M, Nonaka M, Fujii H, Ueta Y, Narita M, Sata N, Yada T, Uezono Y | title = Neuropeptide oxytocin enhances μ opioid receptor signaling as a positive allosteric modulator | journal = J Pharmacol Sci | volume = 137 | issue = 1 | pages = 67–75 | date = May 2018 | pmid = 29716811 | doi = 10.1016/j.jphs.2018.04.002 | url = | doi-access = free }}</ref><ref name="MiyanoYoshidaHirayama2021">{{cite journal | vauthors = Miyano K, Yoshida Y, Hirayama S, Takahashi H, Ono H, Meguro Y, Manabe S, Komatsu A, Nonaka M, Mizuguchi T, Fujii H, Higami Y, Narita M, Uezono Y | title = Oxytocin Is a Positive Allosteric Modulator of κ-Opioid Receptors but Not δ-Opioid Receptors in the G Protein Signaling Pathway | journal = Cells | volume = 10 | issue = 10 | date = October 2021 | page = 2651 | pmid = 34685631 | pmc = 8534029 | doi = 10.3390/cells10102651 | doi-access = free | url = }}</ref><ref name="MizuguchiMiyanoKamauchi2023">{{cite journal | vauthors = Mizuguchi T, Miyano K, Yamauchi R, Yoshida Y, Takahashi H, Yamazaki A, Ono H, Inagaki M, Nonaka M, Uezono Y, Fujii H | title = The first structure-activity relationship study of oxytocin as a positive allosteric modulator for the µ opioid receptor | journal = Peptides | volume = 159 | issue = | article-number = 170901 | date = January 2023 | pmid = 36347314 | doi = 10.1016/j.peptides.2022.170901 | url = }}</ref>

===Physiological{{anchor|Actions within the brain}}===
The [[peripheral]] actions of oxytocin mainly reflect secretion from the pituitary gland. The behavioral effects of oxytocin are thought to reflect release from centrally projecting oxytocin neurons, different from those that project to the pituitary gland, or that are collaterals from them.<ref name="Ross"/> Oxytocin receptors are expressed by neurons in many parts of the brain and spinal cord, including the amygdala, [[ventromedial hypothalamus]], [[septum]], [[nucleus accumbens]], and [[brainstem]], although the distribution differs markedly between species.<ref name=":0" /> Furthermore, the distribution of these receptors changes during development and has been observed to change after [[Birth|parturition]] in the [[montane vole]].<ref name=":0" />

* [[Lactation#Milk ejection reflex|Milk ejection reflex]]/Letdown reflex: in [[lactation|lactating]] ([[breastfeeding]]) mothers, oxytocin acts at the [[mammary gland]]s, causing milk to be 'let down' into [[lactiferous duct]]s, from where it can be excreted via the [[nipple]].<ref>{{EMedicine|article|976504|Human Milk and Lactation}}</ref> Suckling by the infant at the [[nipple]] is relayed by [[spinal nerves]] to the hypothalamus. The stimulation causes neurons that make oxytocin to fire action potentials in intermittent bursts; these bursts result in the secretion of pulses of oxytocin from the neurosecretory [[axon terminal|nerve terminals]] of the pituitary gland.
* [[Uterine contraction]]: important for [[cervical dilation]] before birth, oxytocin causes contractions during the second and third stages of [[labor (childbirth)|labor]].<ref name="MacGill">{{cite web | vauthors = MacGill M | title=What is oxytocin, and what does it do?|url=http://www.medicalnewstoday.com/articles/275795.php|website=Medical News Today|publisher=Heath Line Media|access-date=March 29, 2017}}</ref> Oxytocin release during [[breastfeeding]] causes mild but often painful [[Muscle contraction|contraction]]s during the first few weeks of lactation. This also serves to assist the uterus in clotting the placental attachment point postpartum. However, in [[knockout mouse|knockout mice]] lacking the oxytocin receptor, reproductive behavior and birth are normal.<ref name="Takayanagi">{{cite journal | vauthors = Takayanagi Y, Yoshida M, Bielsky IF, Ross HE, Kawamata M, Onaka T, Yanagisawa T, Kimura T, Matzuk MM, Young LJ, Nishimori K | title = Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 44 | pages = 16096–16101 | date = November 2005 | pmid = 16249339 | pmc = 1276060 | doi = 10.1073/pnas.0505312102 | doi-access = free | bibcode = 2005PNAS..10216096T }}</ref>
*In male rats, oxytocin may induce [[erection]]s.<ref name="ReferenceA">{{cite journal | vauthors = Thackare H, Nicholson HD, Whittington K | title = Oxytocin--its role in male reproduction and new potential therapeutic uses | journal = Human Reproduction Update | volume = 12 | issue = 4 | pages = 437–448 | date = 2006-08-01 | pmid = 16436468 | doi = 10.1093/humupd/dmk002 | doi-access = free }}</ref> A burst of oxytocin is released during ejaculation in several species, including human males; its suggested function is to stimulate contractions of the reproductive tract, aiding [[sperm]] release.<ref name="ReferenceA"/>
* [[Sexual stimulation|Human sexual response]]: Oxytocin levels in [[blood plasma|plasma]] rise during sexual stimulation and orgasm. At least two uncontrolled studies have found increases in plasma oxytocin at orgasm in both men and women.<ref name="carm1987">{{cite journal | vauthors = Carmichael MS, Humbert R, Dixen J, Palmisano G, Greenleaf W, Davidson JM | title = Plasma oxytocin increases in the human sexual response | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 64 | issue = 1 | pages = 27–31 | date = January 1987 | pmid = 3782434 | doi = 10.1210/jcem-64-1-27 }}</ref><ref name="pmid8135652">{{cite journal | vauthors = Carmichael MS, Warburton VL, Dixen J, Davidson JM | title = Relationships among cardiovascular, muscular, and oxytocin responses during human sexual activity | journal = Archives of Sexual Behavior | volume = 23 | issue = 1 | pages = 59–79 | date = February 1994 | pmid = 8135652 | doi = 10.1007/BF01541618 | s2cid = 36539568 }}</ref> Plasma oxytocin levels are increased around the time of self-stimulated orgasm and are still higher than baseline when measured five minutes after self arousal.<ref name="carm1987" /> The authors of one of these studies speculated that oxytocin's effects on muscle contractibility may facilitate sperm and egg transport.<ref name="carm1987" />
:In a study measuring oxytocin serum levels in women before and after [[sexual stimulation]], the author suggests it serves an important role in [[sexual arousal]]. This study found genital tract stimulation resulted in increased oxytocin immediately after orgasm.<ref name="Blaicher1999">{{cite journal | vauthors = Blaicher W, Gruber D, Bieglmayer C, Blaicher AM, Knogler W, Huber JC | title = The role of oxytocin in relation to female sexual arousal | journal = Gynecologic and Obstetric Investigation | volume = 47 | issue = 2 | pages = 125–126 | year = 1999 | pmid = 9949283 | doi = 10.1159/000010075 | s2cid = 43036197 }}</ref> Another study reported increases of oxytocin during sexual arousal could be in response to nipple/areola, genital, and/or genital tract stimulation as confirmed in other mammals.<ref name="Andersonhunt1995">{{cite journal | vauthors = Anderson-Hunt M, Dennerstein L | title = Oxytocin and female sexuality | journal = Gynecologic and Obstetric Investigation | volume = 40 | issue = 4 | pages = 217–221 | year = 1995 | pmid = 8586300 | doi = 10.1159/000292340 }}</ref> Murphy et al. (1987), studying men, found that plasma oxytocin levels remain unchanged during sexual arousal, but that levels increase sharply after ejaculation, returning to baseline levels within 30 minutes. In contrast, vasopressin was increased during arousal but returned to baseline at the time of ejaculation. The study concludes that (in males) vasopressin is secreted during arousal, while oxytocin is only secreted after ejaculation.<ref name="pmid3654918">{{cite journal | vauthors = Murphy MR, Seckl JR, Burton S, Checkley SA, Lightman SL | title = Changes in oxytocin and vasopressin secretion during sexual activity in men | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 65 | issue = 4 | pages = 738–741 | date = October 1987 | pmid = 3654918 | doi = 10.1210/jcem-65-4-738 | doi-access = free }}</ref> A more recent study of men found an increase in plasma oxytocin immediately after orgasm, but only in a portion of their sample that did not reach statistical significance. The authors noted these changes "may simply reflect contractile properties on reproductive tissue".<ref name="pmid12697037">{{cite journal | vauthors = Krüger TH, Haake P, Chereath D, Knapp W, Janssen OE, Exton MS, Schedlowski M, Hartmann U | title = Specificity of the neuroendocrine response to orgasm during sexual arousal in men | journal = The Journal of Endocrinology | volume = 177 | issue = 1 | pages = 57–64 | date = April 2003 | pmid = 12697037 | doi = 10.1677/joe.0.1770057 | doi-access = free }}</ref>
* Due to its similarity to vasopressin, it can reduce the excretion of [[urine]] slightly, and so it can be classified as an [[antidiuretic]]. In several species, oxytocin can stimulate sodium excretion from the kidneys ([[natriuresis]]), and in humans high doses can result in low sodium levels ([[hyponatremia]]).
* Cardiac effects: oxytocin and oxytocin receptors are also found in the heart in some rodents, and the hormone may play a role in the embryonal development of the heart by promoting [[cardiomyocyte]] differentiation.<ref name="pmid12093924">{{cite journal | vauthors = Paquin J, Danalache BA, Jankowski M, McCann SM, Gutkowska J | title = Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 14 | pages = 9550–9555 | date = July 2002 | pmid = 12093924 | pmc = 123178 | doi = 10.1073/pnas.152302499 | doi-access = free | bibcode = 2002PNAS...99.9550P }}</ref><ref name="pmid15316117">{{cite journal | vauthors = Jankowski M, Danalache B, Wang D, Bhat P, Hajjar F, Marcinkiewicz M, Paquin J, McCann SM, Gutkowska J | title = Oxytocin in cardiac ontogeny | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 35 | pages = 13074–13079 | date = August 2004 | pmid = 15316117 | pmc = 516519 | doi = 10.1073/pnas.0405324101 | doi-access = free | bibcode = 2004PNAS..10113074J }}</ref> However, the absence of either oxytocin or its receptor in knockout mice has not been reported to produce cardiac insufficiencies.<ref name="Takayanagi" />
* Modulation of [[hypothalamic-pituitary-adrenal axis]] activity: oxytocin, under certain circumstances, indirectly inhibits release of [[adrenocorticotropic hormone]] and [[cortisol]] and, in those situations, may be considered an antagonist of vasopressin.<ref name="isbn83-200-1415-8">{{cite book | vauthors = Hartwig W | title = Endokrynologia praktyczna | publisher = Państwowy Zakład Wydawnictw Lekarskich  | location = [[Warsaw]] | year = 1989 | isbn = 978-83-200-1415-0 }}{{Page needed|date=September 2010}}</ref>
* Preparing fetal neurons for delivery (in rats): crossing the placenta, maternal oxytocin reaches the fetal brain and induces a switch in the action of neurotransmitter [[GABA]] from excitatory to inhibitory on fetal cortical neurons. This silences the fetal brain for the period of delivery and reduces its vulnerability to [[hypoxia (medical)|hypoxic damage]].<ref name="pmid17170309">{{cite journal | vauthors = Tyzio R, Cossart R, Khalilov I, Minlebaev M, Hübner CA, Represa A, Ben-Ari Y, Khazipov R | title = Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery | journal = Science | volume = 314 | issue = 5806 | pages = 1788–1792 | date = December 2006 | pmid = 17170309 | doi = 10.1126/science.1133212 | s2cid = 85151049 | bibcode = 2006Sci...314.1788T | url = https://www.hal.inserm.fr/inserm-00483930/file/TyzioScience2006.pdf }}</ref>
*Feeding: a 2012 paper suggested that oxytocin neurons in the para-ventricular hypothalamus in the brain may play a key role in suppressing appetite under normal conditions and that other hypothalamic neurons may trigger eating via inhibition of these oxytocin neurons. This population of oxytocin neurons is absent in [[Prader-Willi syndrome]], a genetic disorder that leads to uncontrollable feeding and obesity, and may play a key role in its pathophysiology.<ref>{{cite journal | vauthors = Atasoy D, Betley JN, Su HH, Sternson SM | title = Deconstruction of a neural circuit for hunger | journal = Nature | volume = 488 | issue = 7410 | pages = 172–177 | date = August 2012 | pmid = 22801496 | pmc = 3416931 | doi = 10.1038/nature11270 | bibcode = 2012Natur.488..172A }}</ref> Research on the oxytocin-related neuropeptide asterotocin in [[starfish]] also showed that in echinoderms, the chemical induces muscle relaxation, and in starfish specifically caused the organisms to evert their stomach and react as though feeding on prey, even when none were present.<ref>{{cite journal | vauthors = Odekunle EA, Semmens DC, Martynyuk N, Tinoco AB, Garewal AK, Patel RR, Blowes LM, Zandawala M, Delroisse J, Slade SE, Scrivens JH, Egertová M, Elphick MR | title = Ancient role of vasopressin/oxytocin-type neuropeptides as regulators of feeding revealed in an echinoderm | journal = BMC Biology | volume = 17 | issue = 1 | article-number = 60 | date = July 2019 | pmid = 31362737 | pmc = 6668147 | doi = 10.1186/s12915-019-0680-2 | doi-access = free }}</ref>

===Psychological===
* Autism: Oxytocin has been implicated in the etiology of autism, with one report suggesting autism is correlated to a mutation on the oxytocin receptor gene ([[Oxytocin receptor|''OXTR'']]). Studies involving Caucasian, Finnish and Chinese Han families provide support for the relationship of ''OXTR'' with autism.<ref name="Gregory2009">{{cite journal | vauthors = Jacob S, Brune CW, Carter CS, Leventhal BL, Lord C, Cook EH | title = Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism | journal = Neuroscience Letters | volume = 417 | issue = 1 | pages = 6–9 | date = April 2007 | pmid = 17383819 | pmc = 2705963 | doi = 10.1016/j.neulet.2007.02.001 }}</ref><ref name="Wermter2009">{{cite journal | vauthors = Wermter AK, Kamp-Becker I, Hesse P, Schulte-Körne G, Strauch K, Remschmidt H | title = Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 153B | issue = 2 | pages = 629–639 | date = March 2010 | pmid = 19777562 | doi = 10.1002/ajmg.b.31032 | s2cid = 15970613 }}</ref> Autism may also be associated with an aberrant methylation of ''OXTR''.<ref name="Gregory2009"/> However, evidence has shown that intranasal administration is likely insufficient to produce behavioural effects<ref>{{cite journal | vauthors = Leng G, Ludwig M | title = Intranasal Oxytocin: Myths and Delusions | journal = Biological Psychiatry | volume = 79 | issue = 3 | pages = 243–250 | date = February 2016 | pmid = 26049207 | doi = 10.1016/j.biopsych.2015.05.003 | url = https://www.pure.ed.ac.uk/ws/files/19764306/accepted_manuscript_Leng_and_Ludwig.pdf }}</ref> and it could be explained by publication bias and selective outcome reporting, impacting reproducibility of results.<ref>{{cite journal | vauthors = Audunsdottir K, Sartorius AM, Kang H, Glaser BD, Boen R, Nærland T, Alaerts K, Kildal ES, Westlye LT, Andreassen OA, Quintana DS | title = The effects of oxytocin administration on social and routinized behaviors in autism: A preregistered systematic review and meta-analysis | journal = Psychoneuroendocrinology | volume = 167 | article-number = 107067 | date = September 2024 | pmid = 38815399 | doi = 10.1016/j.psyneuen.2024.107067 | hdl = 10852/115053 | hdl-access = free }}</ref>  In addition, with focus being primarily on animal models that lack translational validity due to autism's complex social and communicative dimensions,<ref>{{cite journal | vauthors = Wilson E, Ramage FJ, Wever KE, Sena ES, Macleod MR, Currie GL | title = Designing, conducting, and reporting reproducible animal experiments | journal = The Journal of Endocrinology | volume = 258 | issue = 1 | date = July 2023 | pmid = 37074416 | pmc = 10304908 | doi = 10.1530/JOE-22-0330 }}</ref> current discussion has challenged the intervention and stated that neurodivergent perspectives need to be considered.<ref>{{cite journal | vauthors = Phan JM, Dwyer P, Elsherif MM, Friedel E, Kapp SK | title = Oxytocin in autism: Rethinking treatment and research through a neurodivergent perspective | journal = Psychoneuroendocrinology | volume = 171 | article-number = 107220 | date = October 2024 | pmid = 39471539 | doi = 10.1016/j.psyneuen.2024.107220 | pmc = 12253975 }}</ref><ref>{{Cite journal | vauthors = Fletcher-Watson S, Brook K, Hallett S, Murray F, Crompton CJ | date = June 2021 |title=Inclusive Practices for Neurodevelopmental Research |journal=Current Developmental Disorders Reports |language=en |volume=8 |issue=2 |pages=88–97 |doi=10.1007/s40474-021-00227-z |issn=2196-2987|doi-access=free }}</ref>
* Protection of brain functions: Studies in rats have demonstrated that nasal application of oxytocin can alleviate impaired learning capabilities caused by restrained stress. The authors attributed this effect to an improved hippocampal response in Brain-Derived Neurotrophic Factor (BDNF) being observed.<ref>{{cite journal | vauthors = Dayi A, Cetin F, Sisman AR, Aksu I, Tas A, Gönenc S, Uysal N | title = The effects of oxytocin on cognitive defect caused by chronic restraint stress applied to adolescent rats and on hippocampal VEGF and BDNF levels | journal = Medical Science Monitor | volume = 21 | pages = 69–75 | date = January 2015 | pmid = 25559382 | pmc = 4294596 | doi = 10.12659/MSM.893159 }}</ref> Accordingly, oxytocin has been shown to promote neural growth in the hippocampus in rats even during swim stress or glucocorticoid administration.<ref>{{cite journal | vauthors = Leuner B, Caponiti JM, Gould E | title = Oxytocin stimulates adult neurogenesis even under conditions of stress and elevated glucocorticoids | journal = Hippocampus | volume = 22 | issue = 4 | pages = 861–868 | date = April 2012 | pmid = 21692136 | pmc = 4756590 | doi = 10.1002/hipo.20947 }}</ref> In a mouse model of early onset of Alzheimer's, the administration of oxytocin by a gel particularly designed to make the peptide accessible for the brain, the cognitive decline and hippocampal atrophy of these mice were delayed. Moreover, the amyloid β-protein deposit and nerve cell apoptosis were retarded. An observed inhibitory impact by oxytocin on the inflammatory activity of the microglia was proposed to be an important factor.<ref>{{cite journal | vauthors = Ye C, Cheng M, Ma L, Zhang T, Sun Z, Yu C, Wang J, Dou Y | title = Oxytocin Nanogels Inhibit Innate Inflammatory Response for Early Intervention in Alzheimer's Disease | journal = ACS Applied Materials & Interfaces | volume = 14 | issue = 19 | pages = 21822–21835 | date = May 2022 | pmid = 35510352 | doi = 10.1021/acsami.2c00007 | bibcode = 2022AAMI...1421822Y | s2cid = 248526969 }}</ref>

====Bonding====
{{missing information|section|{{PMID| 36708707}} on Oxtr knockout voles still somehow bonding|date=December 2023}}
In the [[prairie vole]], oxytocin released into the brain of the female during sexual activity is important for forming a pair bond with her sexual partner. [[Vasopressin]] appears to have a similar effect in males.<ref>{{cite web |url=http://www.americanscientist.org/issues/pub/high-on-fidelity | vauthors = Vacek M |year=2002 |title=High on Fidelity: What can voles teach us about monogamy? |archive-url=https://web.archive.org/web/20061015201214/http://www.americanscientist.org/template/AssetDetail/assetid/14756 |archive-date=October 15, 2006 |work=American Scientist }}</ref> Oxytocin has a role in social behaviors in many species, so it likely also does in humans. In a 2003 study, both humans and dog oxytocin levels in the blood rose after a five to 24 minute petting session. This possibly plays a role in the [[human-canine bond|emotional bonding between humans and dogs]].<ref name="pmid12672376">{{cite journal | vauthors = Odendaal JS, Meintjes RA | title = Neurophysiological correlates of affiliative behaviour between humans and dogs | journal = Veterinary Journal | volume = 165 | issue = 3 | pages = 296–301 | date = May 2003 | pmid = 12672376 | doi = 10.1016/S1090-0233(02)00237-X }}</ref>
* [[Maternal bond|Maternal behavior]]: Female rats given oxytocin [[Receptor antagonist|antagonists]] after giving birth do not exhibit typical maternal behavior.<ref name="pmid3819639">{{cite journal | vauthors = van Leengoed E, Kerker E, Swanson HH | title = Inhibition of post-partum maternal behaviour in the rat by injecting an oxytocin antagonist into the cerebral ventricles | journal = The Journal of Endocrinology | volume = 112 | issue = 2 | pages = 275–282 | date = February 1987 | pmid = 3819639 | doi = 10.1677/joe.0.1120275 }}</ref> By contrast, virgin female sheep show maternal behavior toward foreign lambs upon [[cerebrospinal fluid]] infusion of oxytocin, which they would not do otherwise.<ref name="urlBritish Society for Neuroendocrinology – 22. The Neurobiology of Social Bonds">{{cite journal | vauthors = Kendrick KM | title = The neurobiology of social bonds | journal = Journal of Neuroendocrinology | volume = 16 | issue = 12 | pages = 1007–1008 | date = December 2004 | pmid = 15667456 | doi = 10.1111/j.1365-2826.2004.01262.x | url = http://neuroendo.org.uk/index.php/content/view/34/11/ | access-date = 2009-04-13 | publisher = British Society for Neuroendocrinology | s2cid = 21635457 | archive-url = https://web.archive.org/web/20090429021123/http://neuroendo.org.uk/index.php/content/view/34/11 | archive-date = 2009-04-29 | url-access = subscription }}</ref> Oxytocin is involved in the initiation of human maternal behavior, not its maintenance; for example, it is higher in mothers after they interact with unfamiliar children rather than their own.<ref name="pmid20953313">{{cite journal | vauthors = Bick J, Dozier M | title = Mothers' and Children's Concentrations of Oxytocin Following Close, Physical Interactions with Biological and Non-biological Children | journal = Developmental Psychobiology | volume = 52 | issue = 1 | pages = 100–107 | date = January 2010 | pmid = 20953313 | pmc = 2953948 | doi = 10.1002/dev.20411 }}</ref>
*Human [[ingroup]] bonding: Oxytocin can increase positive attitudes, such as bonding, toward individuals classified as "in-group" members, whereas other individuals become classified as "out-group" members. Oxytocin has also been implicated in [[Lie|lying]] when lying would prove beneficial to other in-group members. In a study where such a relationship was examined, it was found that when individuals were administered oxytocin, rates of [[dishonesty]] in the participants' responses increased for their in-group members when a beneficial outcome for their group was expected.<ref>{{cite journal | vauthors = Shalvi S, De Dreu CK | title = Oxytocin promotes group-serving dishonesty | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 15 | pages = 5503–5507 | date = April 2014 | pmid = 24706799 | pmc = 3992689 | doi = 10.1073/pnas.1400724111 | doi-access = free | bibcode = 2014PNAS..111.5503S }}</ref> Both of these examples show the tendency of individuals to act in ways that benefit those considered to be members of their social group, or in-group.
* Decreased oxytocin  & receptor expression has been associated with aggressive behavior in aggressive-impulsive disorders.<ref>{{cite journal | vauthors = Diaz-Marsá M, López-Villatoro JM, De la Torre-Luque A, MacDowell KS, Galvez-Merlin A, Gómez Del Barrio A, Ruiz-Guerrero F, Beato-Fernández L, Polo-Montes F, León-Velasco M, Martín-Hernández D, Carrasco-Diaz A, Leza JC, Carrasco JL | title = Decreased oxytocin plasma levels and oxytocin receptor expression associated with aggressive behavior in aggressive-impulsive disorders | journal = Journal of Psychiatric Research | volume = 170 | pages = 200–206 | date = February 2024 | pmid = 38157667 | doi = 10.1016/j.jpsychires.2023.12.032 }}</ref>

Oxytocin is not only correlated with the preferences of individuals to associate with members of their own group, but it is also evident during conflicts between members of different groups.  During conflict, individuals receiving nasally administered oxytocin demonstrate more frequent defense-motivated responses toward in-group members than out-group members. Further, oxytocin was correlated with participant desire to protect vulnerable in-group members, despite that individual's attachment to the conflict.<ref name="pmid23144787">{{cite journal | vauthors = De Dreu CK, Shalvi S, Greer LL, Van Kleef GA, Handgraaf MJ | title = Oxytocin motivates non-cooperation in intergroup conflict to protect vulnerable in-group members | journal = PLOS ONE | volume = 7 | issue = 11 | article-number = e46751 | year = 2012 | pmid = 23144787 | pmc = 3492361 | doi = 10.1371/journal.pone.0046751 | doi-access = free | bibcode = 2012PLoSO...746751D }}</ref> Similarly, it has been demonstrated that when oxytocin is administered, individuals alter their subjective preferences in order to align with in-group ideals over out-group ideals.<ref>{{cite journal | vauthors = Stallen M, De Dreu CK, Shalvi S, Smidts A, Sanfey AG | title = The herding hormone: oxytocin stimulates in-group conformity | journal = Psychological Science | volume = 23 | issue = 11 | pages = 1288–1292 | year = 2012 | pmid = 22991128 | doi = 10.1177/0956797612446026 | s2cid = 16255677 | hdl = 2066/121872 | hdl-access = free }}</ref> These studies demonstrate that oxytocin is associated with intergroup dynamics.  Further, oxytocin influences the responses of individuals in a particular group to those of another group. The in-group bias is evident in smaller groups; however, it can also be extended to groups as large as one's entire country leading toward a tendency of strong national zeal. A study done in the Netherlands showed that oxytocin increased the in-group favoritism of their nation while decreasing acceptance of members of other ethnicities and foreigners.<ref name="pmid21220339"/> People also show more affection for their country's flag while remaining indifferent to other cultural objects when exposed to oxytocin.<ref name="pmid25140135">{{cite journal | vauthors = Ma X, Luo L, Geng Y, Zhao W, Zhang Q, Kendrick KM | title = Oxytocin increases liking for a country's people and national flag but not for other cultural symbols or consumer products | journal = Frontiers in Behavioral Neuroscience | volume = 8 | page = 266 | year = 2014 | pmid = 25140135 | pmc = 4122242 | doi = 10.3389/fnbeh.2014.00266 | doi-access = free }}</ref> It has thus been hypothesized that this hormone may be a factor in [[xenophobic]] tendencies secondary to this effect.  Thus, oxytocin appears to affect individuals at an international level where the in-group becomes a specific "home" country and the out-group grows to include all other countries.

====Drugs====
* [[Drug interaction]]: According to several studies in animals, oxytocin inhibits the development of [[Drug tolerance|tolerance]] to various addictive drugs ([[opiate]]s, [[cocaine]], [[ethanol|alcohol]]), and reduces [[Drug withdrawal|withdrawal]] symptoms.<ref name="pmid9924746">{{cite journal | vauthors = Kovács GL, Sarnyai Z, Szabó G | title = Oxytocin and addiction: a review | journal = Psychoneuroendocrinology | volume = 23 | issue = 8 | pages = 945–962 | date = November 1998 | pmid = 9924746 | doi = 10.1016/S0306-4530(98)00064-X | s2cid = 31674417 }}</ref> [[MDMA]] (ecstasy) may increase feelings of love, empathy, and connection to others by stimulating oxytocin activity primarily via activation of [[serotonin]] [[5-HT1A receptor]]s, if initial studies in animals apply to humans.<ref name="pmid17383105">{{cite journal | vauthors = Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS | title = A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy") | journal = Neuroscience | volume = 146 | issue = 2 | pages = 509–514 | date = May 2007 | pmid = 17383105 | doi = 10.1016/j.neuroscience.2007.02.032 | s2cid = 15617471 }}</ref> The [[anxiolytic]] drug [[buspirone]] may produce some of its effects via 5-HT1A receptor-induced oxytocin stimulation as well.<ref name="pmid9025112">{{cite journal | vauthors = Uvnäs-Moberg K, Hillegaart V, Alster P, Ahlenius S | title = Effects of 5-HT agonists, selective for different receptor subtypes, on oxytocin, CCK, gastrin and somatostatin plasma levels in the rat | journal = Neuropharmacology | volume = 35 | issue = 11 | pages = 1635–1640 | year = 1996 | pmid = 9025112 | doi = 10.1016/S0028-3908(96)00078-0 | s2cid = 44375951 }}</ref><ref name="pmid8771561">{{cite journal | vauthors = Chiodera P, Volpi R, Capretti L, Caffarri G, Magotti MG, Coiro V | title = Different effects of the serotonergic agonists buspirone and sumatriptan on the posterior pituitary hormonal responses to hypoglycemia in humans | journal = Neuropeptides | volume = 30 | issue = 2 | pages = 187–192 | date = April 1996 | pmid = 8771561 | doi = 10.1016/S0143-4179(96)90086-4 | s2cid = 13734738 }}</ref>
* [[Addiction vulnerability]]: Concentrations of endogenous oxytocin can impact the effects of various drugs and one's susceptibility to [[substance use disorder]]s, with higher concentrations associated with lower susceptibility. The status of the endogenous oxytocin system can enhance or reduce susceptibility to addiction through its bidirectional interaction with numerous systems, including the [[dopamine]] system, the [[hypothalamic–pituitary–adrenal axis]] and the [[immune system]]. Individual differences in the endogenous oxytocin system based on genetic predisposition, gender and environmental influences, may therefore affect [[addiction vulnerability]].<ref name="PBB">{{cite journal | vauthors = Buisman-Pijlman FT, Sumracki NM, Gordon JJ, Hull PR, Carter CS, Tops M | title = Individual differences underlying susceptibility to addiction: Role for the endogenous oxytocin system | journal = Pharmacology, Biochemistry, and Behavior | volume = 119 | pages = 22–38 | date = April 2014 | pmid = 24056025 | doi = 10.1016/j.pbb.2013.09.005 | doi-access = free | hdl = 1871.1/d0f0f74d-0c63-40c3-8ac9-57e20af38cf4 | hdl-access = free }}</ref> Oxytocin may be related to the [[Conditioned place preference|place conditioning behaviors]] observed in habitual drug abusers.

====Fear and anxiety====
Oxytocin is typically remembered for the effect it has on [[prosocial behavior]]s, such as its role in facilitating trust and attachment between individuals.<ref name="Grillon 958–960">{{cite journal | vauthors = Grillon C, Krimsky M, Charney DR, Vytal K, Ernst M, Cornwell B | title = Oxytocin increases anxiety to unpredictable threat | journal = Molecular Psychiatry | volume = 18 | issue = 9 | pages = 958–960 | date = September 2013 | pmid = 23147382 | pmc = 3930442 | doi = 10.1038/mp.2012.156 }}</ref>{{qualify evidence}} However, oxytocin has a more complex role than solely enhancing prosocial behaviors. There is consensus that oxytocin modulates [[fear]] and [[anxiety]]; that is, it does not directly elicit fear or anxiety.<ref name="Guzmán 1185–1187">{{cite journal | vauthors = Guzmán YF, Tronson NC, Jovasevic V, Sato K, Guedea AL, Mizukami H, Nishimori K, Radulovic J | title = Fear-enhancing effects of septal oxytocin receptors | journal = Nature Neuroscience | volume = 16 | issue = 9 | pages = 1185–1187 | date = September 2013 | pmid = 23872596 | pmc = 3758455 | doi = 10.1038/nn.3465 }}</ref> Two dominant theories explain the role of oxytocin in fear and anxiety. One theory states that oxytocin increases approach/avoidance to certain social stimuli and the second theory states that oxytocin increases the salience of certain social stimuli, causing animals (including humans) to pay closer attention to socially relevant stimuli.<ref name="Theodoridou e58113">{{cite journal | vauthors = Theodoridou A, Penton-Voak IS, Rowe AC | title = A direct examination of the effect of intranasal administration of oxytocin on approach-avoidance motor responses to emotional stimuli | journal = PLOS ONE | volume = 8 | issue = 2 | article-number = e58113 | year = 2013 | pmid = 23469148 | pmc = 3585234 | doi = 10.1371/journal.pone.0058113 | doi-access = free | bibcode = 2013PLoSO...858113T }}</ref><ref>Ibukun Akinrinade, Kyriacos Kareklas, Magda C. Teles, Thais K. Reis, Michael Gliksberg, Giovanni Petri, Gil Levkowitz, Rui F. Oliveira, ''[https://www.science.org/doi/10.1126/science.abq5158 Evolutionarily conserved role of oxytocin in social fear contagion in zebrafish]'', [[Science (magazine)]], March 23, 2023</ref><ref>Larson, Christina, ''[https://apnews.com/article/empathy-zebrafish-oxytocin-origins-800d30fd9058df836e12e70cf5311b9f A fish can sense another's fear, a study shows]'', [[Associated Press]], March 23, 2023</ref>

Nasally administered oxytocin has been reported to reduce [[fear]], possibly by inhibiting the [[amygdala]] (which is thought to be responsible for fear responses).<ref name="pmid16339042">{{cite journal | vauthors = Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A | title = Oxytocin modulates neural circuitry for social cognition and fear in humans | journal = The Journal of Neuroscience | volume = 25 | issue = 49 | pages = 11489–11493 | date = December 2005 | pmid = 16339042 | pmc = 6725903 | doi = 10.1523/JNEUROSCI.3984-05.2005 }}</ref> Indeed, studies in rodents have shown oxytocin can efficiently inhibit fear responses by activating an inhibitory circuit within the amygdala.<ref name="pmid15821089">{{cite journal | vauthors = Huber D, Veinante P, Stoop R | title = Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala | journal = Science | volume = 308 | issue = 5719 | pages = 245–248 | date = April 2005 | pmid = 15821089 | doi = 10.1126/SCIENCE.1105636 | s2cid = 40887741 | bibcode = 2005Sci...308..245H }}</ref><ref name="pmid21719680">{{cite journal | vauthors = Viviani D, Charlet A, van den Burg E, Robinet C, Hurni N, Abatis M, Magara F, Stoop R | title = Oxytocin selectively gates fear responses through distinct outputs from the central amygdala | journal = Science | volume = 333 | issue = 6038 | pages = 104–107 | date = July 2011 | pmid = 21719680 | doi = 10.1126/SCIENCE.1201043 | s2cid = 20446890 | bibcode = 2011Sci...333..104V }}</ref> Some researchers have argued oxytocin has a general enhancing effect on all social emotions, since intranasal administration of oxytocin also increases [[envy]] and ''[[Schadenfreude]]''.<ref>{{cite journal | vauthors = Shamay-Tsoory SG, Fischer M, Dvash J, Harari H, Perach-Bloom N, Levkovitz Y | title = Intranasal administration of oxytocin increases envy and schadenfreude (gloating) | journal = Biological Psychiatry | volume = 66 | issue = 9 | pages = 864–870 | date = November 2009 | pmid = 19640508 | doi = 10.1016/j.biopsych.2009.06.009 | s2cid = 20396036 }}</ref> Individuals who receive an intranasal dose of oxytocin identify facial expressions of disgust more quickly than individuals who do not receive oxytocin.<ref name="Theodoridou e58113"/>{{qualify evidence}} Facial expressions of disgust are evolutionarily linked to the idea of contagion. Thus, oxytocin increases the salience of cues that imply contamination, which leads to a faster response because these cues are especially relevant for survival. In another study, after administration of oxytocin, individuals displayed an enhanced ability to recognize expressions of fear compared to the individuals who received the placebo.<ref name="pmid19747930">{{cite journal | vauthors = Fischer-Shofty M, Shamay-Tsoory SG, Harari H, Levkovitz Y | title = The effect of intranasal administration of oxytocin on fear recognition | journal = Neuropsychologia | volume = 48 | issue = 1 | pages = 179–184 | date = January 2010 | pmid = 19747930 | doi = 10.1016/j.neuropsychologia.2009.09.003 | s2cid = 34778485 }}</ref> Oxytocin modulates fear responses by enhancing the maintenance of social memories. Rats who are genetically modified to have a surplus of oxytocin receptors display a greater fear response to a previously conditioned stressor. Oxytocin enhances the aversive social memory, leading the rat to display a greater fear response when the aversive stimulus is encountered again.<ref name="Guzmán 1185–1187"/>

====Mood and depression====
Oxytocin produces [[antidepressant]]-like effects in [[animal model]]s of [[depression (mood)|depression]],<ref name="MatsuzakiMatsushita2012">{{cite journal | vauthors = Matsuzaki M, Matsushita H, Tomizawa K, Matsui H | title = Oxytocin: a therapeutic target for mental disorders | journal = The Journal of Physiological Sciences | volume = 62 | issue = 6 | pages = 441–444 | date = November 2012 | pmid = 23007624 | doi = 10.1007/s12576-012-0232-9 | pmc = 10717158 | s2cid = 17860416 | doi-access = free }}</ref> and a deficit of it may be involved in the [[pathophysiology]] of depression in humans.<ref name="McQuaidMcInnis2014">{{cite journal | vauthors = McQuaid RJ, McInnis OA, Abizaid A, Anisman H | title = Making room for oxytocin in understanding depression | journal = Neuroscience and Biobehavioral Reviews | volume = 45 | pages = 305–322 | date = September 2014 | pmid = 25025656 | doi = 10.1016/j.neubiorev.2014.07.005 | s2cid = 32062939 }}</ref> The antidepressant-like effects of oxytocin are not blocked by a selective antagonist of the oxytocin receptor, suggesting that these effects are not mediated by the oxytocin receptor.<ref name="Acevedo-RodriguezMani2015">{{cite journal | vauthors = Acevedo-Rodriguez A, Mani SK, Handa RJ | title = Oxytocin and Estrogen Receptor β in the Brain: An Overview | journal = Frontiers in Endocrinology | volume = 6 | page = 160 | year = 2015 | pmid = 26528239 | pmc = 4606117 | doi = 10.3389/fendo.2015.00160 | doi-access = free }}</ref> In accordance, unlike oxytocin, the selective non-peptide oxytocin receptor agonist [[WAY-267,464]] does not produce antidepressant-like effects, at least in the [[tail suspension test]].<ref name="ShalevEbstein2015">{{cite book | vauthors = Shalev I, Ebstein RP | title = Social Hormones and Human Behavior: What Do We Know and Where Do We Go from Here | url = https://books.google.com/books?id=QbA9CgAAQBAJ&pg=PA51 | year =2015 | publisher = Frontiers Media SA | isbn = 978-2-88919-407-0 | pages = 51–}}</ref> In contrast to WAY-267,464, [[carbetocin]], a close [[structural analog|analogue]] of oxytocin and peptide oxytocin receptor agonist, notably does produce antidepressant-like effects in animals.<ref name="ShalevEbstein2015" /> As such, the antidepressant-like effects of oxytocin may be mediated by modulation of a different target, perhaps the [[arginine vasopressin receptor 1A|vasopressin V<sub>1A</sub> receptor]] where oxytocin is known to weakly bind as an agonist.<ref name="HicksRamos2014">{{cite journal | vauthors = Hicks C, Ramos L, Reekie T, Misagh GH, Narlawar R, Kassiou M, McGregor IS | title = Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non-peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats | journal = British Journal of Pharmacology | volume = 171 | issue = 11 | pages = 2868–2887 | date = June 2014 | pmid = 24641248 | pmc = 4243861 | doi = 10.1111/bph.12613 }}</ref><ref name="ManningMisicka2012">{{cite journal | vauthors = Manning M, Misicka A, Olma A, Bankowski K, Stoev S, Chini B, Durroux T, Mouillac B, Corbani M, Guillon G | title = Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics | journal = Journal of Neuroendocrinology | volume = 24 | issue = 4 | pages = 609–628 | date = April 2012 | pmid = 22375852 | pmc = 3490377 | doi = 10.1111/j.1365-2826.2012.02303.x }}</ref>

Oxytocin mediates the antidepressant-like effects of sexual activity.<ref>{{cite journal | vauthors = Matsushita H, Tomizawa K, Okimoto N, Nishiki T, Ohmori I, Matsui H | title = Oxytocin mediates the antidepressant effects of mating behavior in male mice | journal = Neuroscience Research | volume = 68 | issue = 2 | pages = 151–153 | date = October 2010 | pmid = 20600375 | doi = 10.1016/j.neures.2010.06.007 | s2cid = 207152048 | url = http://ousar.lib.okayama-u.ac.jp/48422 | url-access = subscription }}</ref><ref>{{cite journal | vauthors = Phan J, Alhassen L, Argelagos A, Alhassen W, Vachirakorntong B, Lin Z, Sanathara N, Alachkar A | title = Mating and parenting experiences sculpture mood-modulating effects of oxytocin-MCH signaling | journal = Scientific Reports | volume = 10 | issue = 1 | article-number = 13611 | date = August 2020 | pmid = 32788646 | doi = 10.1038/s41598-020-70667-x | pmc = 7423941 | bibcode = 2020NatSR..1013611P }}</ref> A drug for [[sexual dysfunction]], [[sildenafil]] enhances electrically evoked oxytocin release from the [[pituitary gland]].<ref>{{cite journal | vauthors = Zhang Z, Klyachko V, Jackson MB | title = Blockade of phosphodiesterase Type 5 enhances rat neurohypophysial excitability and electrically evoked oxytocin release | journal = The Journal of Physiology | volume = 584 | issue = Pt 1 | pages = 137–147 | date = October 2007 | pmid = 17690141 | pmc = 2277045 | doi = 10.1113/jphysiol.2007.139303 }}</ref> In accordance, it may have promise as an antidepressant.<ref name="MatsuzakiMatsushita2012" /><ref>{{cite journal | vauthors = Matsushita H, Matsuzaki M, Han XJ, Nishiki TI, Ohmori I, Michiue H, Matsui H, Tomizawa K | title = Antidepressant-like effect of sildenafil through oxytocin-dependent cyclic AMP response element-binding protein phosphorylation | journal = Neuroscience | volume = 200 | pages = 13–18 | date = January 2012 | pmid = 22088430 | doi = 10.1016/j.neuroscience.2011.11.001 | s2cid = 12502639 }}</ref>

==== Sex differences====
In humans, it has been shown that oxytocin differentially affects males and females. Females who are administered oxytocin are overall faster in responding to socially relevant stimuli than males who received oxytocin.<ref name="Theodoridou e58113"/><ref name="Lischke 1431–1438">{{cite journal | vauthors = Lischke A, Gamer M, Berger C, Grossmann A, Hauenstein K, Heinrichs M, Herpertz SC, Domes G | title = Oxytocin increases amygdala reactivity to threatening scenes in females | journal = Psychoneuroendocrinology | volume = 37 | issue = 9 | pages = 1431–1438 | date = September 2012 | pmid = 22365820 | doi = 10.1016/j.psyneuen.2012.01.011 | s2cid = 7981815 }}</ref> Additionally, after the administration of oxytocin, females show increased [[amygdala]] activity in response to threatening scenes; however, males do not show increased amygdala activation. This phenomenon can be explained by looking at the role of [[gonadal hormones]], specifically [[estrogen]], which modulate the enhanced threat processing seen in females. Estrogen has been shown to stimulate the release of oxytocin from the [[hypothalamus]] and promote receptor binding in the amygdala.<ref name="Lischke 1431–1438"/>

It has also been shown that testosterone directly suppresses oxytocin in mice.<ref>{{cite journal | vauthors = Okabe S, Kitano K, Nagasawa M, Mogi K, Kikusui T | title = Testosterone inhibits facilitating effects of parenting experience on parental behavior and the oxytocin neural system in mice | journal = Physiology & Behavior | volume = 118 | pages = 159–164 | date = June 2013 | pmid = 23685236 | doi = 10.1016/j.physbeh.2013.05.017 | s2cid = 46790892 }}</ref> This has been hypothesized to have evolutionary significance. With oxytocin suppressed, activities such as hunting and attacking invaders would be less mentally difficult as oxytocin is strongly associated with empathy.<ref name="pmid20371820"/>

====Social====
Because oxytocin plays a role in social bonding, maternal behaviors and emotional connections between people, it is also informally referred to as the "love hormone".<ref>{{Cite web |date=2021-07-20 |title=Oxytocin: The love hormone |url=https://www.health.harvard.edu/mind-and-mood/oxytocin-the-love-hormone |access-date=2023-11-01 |website=Harvard Health |language=en}}</ref> This term is not a medical or scientific name but is often used to describe oxytocin's effects on human behavior and emotions.
* Affecting [[generosity]] by increasing empathy during perspective taking: In a [[neuroeconomics]] experiment, [[intranasal]] oxytocin increased generosity in the [[Ultimatum Game]] by 80%, but had no effect in the [[Dictator Game]] that measures altruism. Perspective-taking is not required in the Dictator Game, but the researchers in this experiment explicitly induced perspective-taking in the Ultimatum Game by not identifying to participants into which role they would be placed.<ref name="pmid17987115">{{cite journal | vauthors = Zak PJ, Stanton AA, Ahmadi S | title = Oxytocin increases generosity in humans | journal = PLOS ONE | volume = 2 | issue = 11 | article-number = e1128 | date = November 2007 | pmid = 17987115 | pmc = 2040517 | doi = 10.1371/journal.pone.0001128 | veditors = Brosnan S | doi-access = free | bibcode = 2007PLoSO...2.1128Z }}</ref> Serious methodological questions have arisen, however, with regard to the role of oxytocin in trust and generosity.<ref>{{Cite journal|author=Conlisk J |title=Professor Zak's empirical studies on trust and oxytocin |journal=J Econ Behav Organizat |volume=78 |issue=1–2 |pages=160–66 |year=2011|doi=10.1016/j.jebo.2011.01.002}}</ref> Empathy in healthy males has been shown to be increased after intranasal oxytocin<ref name="pmid20371820">{{cite journal | vauthors = Hurlemann R, Patin A, Onur OA, Cohen MX, Baumgartner T, Metzler S, Dziobek I, Gallinat J, Wagner M, Maier W, Kendrick KM | title = Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans | journal = The Journal of Neuroscience | volume = 30 | issue = 14 | pages = 4999–5007 | date = April 2010 | pmid = 20371820 | pmc = 6632777 | doi = 10.1523/JNEUROSCI.5538-09.2010 }}</ref><ref name="pmid17137561">{{cite journal | vauthors = Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC | title = Oxytocin improves "mind-reading" in humans | journal = Biological Psychiatry | volume = 61 | issue = 6 | pages = 731–733 | date = March 2007 | pmid = 17137561 | doi = 10.1016/j.biopsych.2006.07.015 | s2cid = 3125539 }}</ref> This is most likely due to the effect of oxytocin in enhancing eye gaze.<ref name=" Guastellab2008">{{cite journal | vauthors = Guastella AJ, Mitchell PB, Dadds MR | title = Oxytocin increases gaze to the eye region of human faces | journal = Biological Psychiatry | volume = 63 | issue = 1 | pages = 3–5 | date = January 2008 | pmid = 17888410 | doi = 10.1016/j.biopsych.2007.06.026 | s2cid = 11974058 }}</ref> There is some discussion about which aspect of empathy oxytocin might alter – for example, cognitive vs. emotional empathy.<ref name="pmid19102589">{{cite journal | vauthors = Singer T, Snozzi R, Bird G, Petrovic P, Silani G, Heinrichs M, Dolan RJ | title = Effects of oxytocin and prosocial behavior on brain responses to direct and vicariously experienced pain | journal = Emotion | volume = 8 | issue = 6 | pages = 781–791 | date = December 2008 | pmid = 19102589 | pmc = 2672051 | doi = 10.1037/a0014195 }}</ref> While studying wild chimpanzees, it was noted that after a chimpanzee shared food with a non-kin related chimpanzee,  the subjects' levels of oxytocin increased, as measured through their urine. In comparison to other cooperative activities between chimpanzees that were monitored including grooming, food sharing generated higher levels of oxytocin. This comparatively higher level of oxytocin after food sharing parallels the increased level of oxytocin in nursing mothers, sharing nutrients with their kin.<ref>{{cite journal | vauthors = Wittig RM, Crockford C, Deschner T, Langergraber KE, Ziegler TE, Zuberbühler K | title = Food sharing is linked to urinary oxytocin levels and bonding in related and unrelated wild chimpanzees | journal = Proceedings. Biological Sciences | volume = 281 | issue = 1778 | article-number = 20133096 | date = March 2014 | pmid = 24430853 | pmc = 3906952 | doi = 10.1098/rspb.2013.3096 }}</ref> 
* [[Trust (social sciences)|Trust]] is increased by oxytocin.<ref name="pmid15931222">{{cite journal | vauthors = Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E | title = Oxytocin increases trust in humans | journal = Nature | volume = 435 | issue = 7042 | pages = 673–676 | date = June 2005 | pmid = 15931222 | doi = 10.1038/nature03701 | s2cid = 1234727 | bibcode = 2005Natur.435..673K | url = https://archive-ouverte.unige.ch/unige:101739 }}</ref><ref name="Theodoridou_2009">{{cite journal | vauthors = Theodoridou A, Rowe AC, Penton-Voak IS, Rogers PJ | title = Oxytocin and social perception: oxytocin increases perceived facial trustworthiness and attractiveness | journal = Hormones and Behavior | volume = 56 | issue = 1 | pages = 128–132 | date = June 2009 | pmid = 19344725 | doi = 10.1016/j.yhbeh.2009.03.019 | s2cid = 12639878 }}</ref><ref name="Lane_2013">{{cite journal | vauthors = Lane A, Luminet O, Rimé B, Gross JJ, de Timary P, Mikolajczak M | title = Oxytocin increases willingness to socially share one's emotions | journal = International Journal of Psychology | volume = 48 | issue = 4 | pages = 676–681 | year = 2013 | pmid = 22554106 | doi = 10.1080/00207594.2012.677540 | hdl = 2078.1/106864 | hdl-access = free }}</ref><ref name="Cardoso_2013">{{cite journal | vauthors = Cardoso C, Ellenbogen MA, Serravalle L, Linnen AM | title = Stress-induced negative mood moderates the relation between oxytocin administration and trust: evidence for the tend-and-befriend response to stress? | journal = Psychoneuroendocrinology | volume = 38 | issue = 11 | pages = 2800–2804 | date = November 2013 | pmid = 23768973 | doi = 10.1016/j.psyneuen.2013.05.006 | s2cid = 25090544 }}</ref> Study found that with the oxytocin nasal spray, people place more trust to strangers in handling their money.<ref name="pmid15931222"/><ref>{{Cite news | vauthors = Carey B |date=2005-06-02 |title=Hormone Dose May Increase People's Trust in Strangers |language=en-US |work=The New York Times |url=https://www.nytimes.com/2005/06/02/science/hormone-dose-may-increase-peoples-trust-in-strangers.html |access-date=2022-07-22 |issn=0362-4331}}</ref> Disclosure of emotional events is a sign of trust in humans. When recounting a negative event, humans who receive [[intranasal]] oxytocin share more emotional details and stories with more emotional significance.<ref name="Lane_2013" /> Humans also find faces more trustworthy after receiving intranasal oxytocin. In a study, participants who received intranasal oxytocin viewed photographs of human faces with neutral expressions and found them to be more trustworthy than those who did not receive oxytocin.<ref name="Theodoridou_2009" /> This may be because oxytocin reduces the fear of social betrayal in humans.<ref name="pmid18498743">{{cite journal | vauthors = Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E | title = Oxytocin shapes the neural circuitry of trust and trust adaptation in humans | journal = Neuron | volume = 58 | issue = 4 | pages = 639–650 | date = May 2008 | pmid = 18498743 | doi = 10.1016/j.neuron.2008.04.009 | s2cid = 1432797 | doi-access = free }}</ref> Even after experiencing social alienation by being excluded from a conversation, humans who received oxytocin scored higher in trust on the [[Revised NEO Personality Inventory]].<ref name="Cardoso_2013" />  Moreover, in a risky investment game, experimental subjects given nasally administered oxytocin displayed "the highest level of trust" twice as often as the control group. Subjects who were told they were interacting with a computer showed no such reaction, leading to the conclusion that oxytocin was not merely affecting [[risk aversion]].<ref name="pmid15931222"/> When there is a reason to be distrustful, such as experiencing betrayal, differing reactions are associated with [[oxytocin receptor]] [[gene]] ([[OXTR]]) differences. Those with the CT [[haplotype]] {{Clarify|date=April 2020}} experience a stronger reaction, in the form of anger, to betrayal.<ref name="pmid23547247">{{cite journal | vauthors = Tabak BA, McCullough ME, Carver CS, Pedersen EJ, Cuccaro ML | title = Variation in oxytocin receptor gene (OXTR) polymorphisms is associated with emotional and behavioral reactions to betrayal | journal = Social Cognitive and Affective Neuroscience | volume = 9 | issue = 6 | pages = 810–816 | date = June 2014 | pmid = 23547247 | pmc = 4040089 | doi = 10.1093/scan/nst042 }}</ref>
* [[Romance (love)|Romantic attachment]]: In some studies, high levels of [[blood plasma|plasma]] oxytocin have been correlated with romantic attachment. For example, if a couple is separated for a long period of time, anxiety can increase due to the lack of physical affection. Oxytocin may aid romantically attached couples by increasing feelings of anxiety during separation.<ref name="pmid17034623"/>
*Group-serving dishonesty/deception: In a carefully controlled study exploring the biological roots of immoral behavior, oxytocin was shown to promote dishonesty when the outcome favored the group to which an individual belonged instead of just the individual.<ref>{{cite journal | vauthors = Shalvi S, De Dreu CK | title = Oxytocin promotes group-serving dishonesty | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 15 | pages = 5503–5507 | date = April 2014 | pmid = 24706799 | pmc = 3992689 | doi = 10.1073/pnas.1400724111 | doi-access = free | bibcode = 2014PNAS..111.5503S}}
*{{cite news |author=Melissa Hogenboom |date=2 April 2014 |title='Love drug' makes group members lie more |work=BBC News |url=https://www.bbc.com/news/science-environment-26771703}}</ref>
* Oxytocin affects [[social behavior|social]] distance between adult males and females, and may be responsible at least in part for [[romance (love)|romantic attraction]] and subsequent [[monogamy|monogamous]] pair bonding. An oxytocin nasal spray caused men in a monogamous relationship, but not single men, to increase the distance between themselves and an attractive woman during a first encounter by 10 to 15 centimeters. The researchers suggested that oxytocin may help promote fidelity within monogamous relationships.<ref name="pmid23152592">{{cite journal | vauthors = Scheele D, Striepens N, Güntürkün O, Deutschländer S, Maier W, Kendrick KM, Hurlemann R | title = Oxytocin modulates social distance between males and females | journal = The Journal of Neuroscience | volume = 32 | issue = 46 | pages = 16074–16079 | date = November 2012 | pmid = 23152592 | pmc = 6794013 | doi = 10.1523/JNEUROSCI.2755-12.2012 }}</ref> For this reason, it is sometimes referred to as the "bonding hormone". There is some evidence that oxytocin promotes [[ethnocentric]] behavior, incorporating the trust and empathy of [[Ingroups and outgroups|in-groups]] with their suspicion and rejection of outsiders.<ref name="pmid21220339">{{cite journal | vauthors = De Dreu CK, Greer LL, Van Kleef GA, Shalvi S, Handgraaf MJ | title = Oxytocin promotes human ethnocentrism | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 4 | pages = 1262–1266 | date = January 2011 | pmid = 21220339 | pmc = 3029708 | doi = 10.1073/pnas.1015316108 | doi-access = free | bibcode = 2011PNAS..108.1262D }}</ref> Furthermore, genetic differences in the [[oxytocin receptor]] gene (OXTR) have been associated with maladaptive social traits such as aggressive behavior.<ref name="pmid22372486">{{cite journal | vauthors = Malik AI, Zai CC, Abu Z, Nowrouzi B, Beitchman JH | title = The role of oxytocin and oxytocin receptor gene variants in childhood-onset aggression | journal = Genes, Brain and Behavior | volume = 11 | issue = 5 | pages = 545–551 | date = July 2012 | pmid = 22372486 | doi = 10.1111/j.1601-183X.2012.00776.x | s2cid = 38807759 | doi-access = free }}</ref>
* [[Social behavior]]<ref name="pmid21220339"/><ref name="pmid15677415">{{cite journal | vauthors = Zak PJ, Kurzban R, Matzner WT | title = The neurobiology of trust | journal = Annals of the New York Academy of Sciences | volume = 1032 | issue = 1 | pages = 224–227 | date = December 2004 | pmid = 15677415 | doi = 10.1196/annals.1314.025 | s2cid = 45599465 | bibcode = 2004NYASA1032..224Z }}</ref> and [[wound healing]]: Oxytocin is also thought to modulate [[inflammation]] by decreasing certain [[cytokines]].<ref>{{cite journal | vauthors = Buemann B, Marazziti D, Uvnäs-Moberg K | title = Can intravenous oxytocin infusion counteract hyperinflammation in COVID-19 infected patients? | journal = The World Journal of Biological Psychiatry | volume = 22 | issue = 5 | pages = 387–398 | date = June 2021 | pmid = 32914674 | doi = 10.1080/15622975.2020.1814408 | s2cid = 221623635 | doi-access = free }}</ref> Thus, the increased release in oxytocin following positive social interactions has the potential to improve wound healing. A study by Marazziti and colleagues used heterosexual couples to investigate this possibility. They found increases in plasma oxytocin following a social interaction were correlated with faster wound healing. They hypothesized this was due to oxytocin reducing inflammation, thus allowing the wound to heal more quickly. This study provides preliminary evidence that positive social interactions may directly influence aspects of health.<ref>{{cite journal | vauthors = Gouin JP, Carter CS, Pournajafi-Nazarloo H, Glaser R, Malarkey WB, Loving TJ, Stowell J, Kiecolt-Glaser JK | title = Marital behavior, oxytocin, vasopressin, and wound healing | journal = Psychoneuroendocrinology | volume = 35 | issue = 7 | pages = 1082–1090 | date = August 2010 | pmid = 20144509 | pmc = 2888874 | doi = 10.1016/j.psyneuen.2010.01.009 }}</ref>
* According to a study published in 2014, silencing of oxytocin receptor interneurons in the medial prefrontal cortex (mPFC) of female mice resulted in loss of social interest in male mice during the sexually receptive phase of the estrous cycle.<ref name="pmid25303526">{{cite journal | vauthors = Nakajima M, Görlich A, Heintz N | title = Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons | journal = Cell | volume = 159 | issue = 2 | pages = 295–305 | date = October 2014 | pmid = 25303526 | pmc = 4206218 | doi = 10.1016/j.cell.2014.09.020 }}
*{{cite web |author=Marie-Therese Walsh |date=2014-10-09 |title="Love Hormone" Oxytocin Regulates Sociosexual Behavior in Female Mice |website=SciGuru |url=http://www.sciguru.org/newsitem/17672/love-hormone-oxycotin-regulates-sociosexual-behavior-female-mice |archive-url=https://web.archive.org/web/20141013144555/http://www.sciguru.org/newsitem/17672/love-hormone-oxycotin-regulates-sociosexual-behavior-female-mice |archive-date=2014-10-13}}</ref> Oxytocin evokes feelings of contentment, reductions in anxiety, and feelings of calmness and security when in the company of the mate.<ref name="pmid17034623">{{cite journal | vauthors = Marazziti D, Dell'Osso B, Baroni S, Mungai F, Catena M, Rucci P, Albanese F, Giannaccini G, Betti L, Fabbrini L, Italiani P, Del Debbio A, Lucacchini A, Dell'Osso L | title = A relationship between oxytocin and anxiety of romantic attachment | journal = Clinical Practice and Epidemiology in Mental Health | volume = 2 | issue = 1 | page = 28 | date = October 2006 | pmid = 17034623 | pmc = 1621060 | doi = 10.1186/1745-0179-2-28 | doi-access = free }}</ref> This suggests oxytocin may be important for the inhibition of the brain regions associated with behavioral control, fear, and anxiety, thus allowing orgasm to occur. Research has also demonstrated that oxytocin can decrease anxiety and protect against [[Stress (biology)|stress]], particularly in combination with social support.<ref name="pmid14675803">{{cite journal | vauthors = Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U | title = Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress | journal = Biological Psychiatry | volume = 54 | issue = 12 | pages = 1389–1398 | date = December 2003 | pmid = 14675803 | doi = 10.1016/S0006-3223(03)00465-7 | s2cid = 20632786 }}</ref><ref>{{cite journal | vauthors = Matsushita H, Latt HM, Koga Y, Nishiki T, Matsui H | title = Oxytocin and Stress: Neural Mechanisms, Stress-Related Disorders, and Therapeutic Approaches | journal = Neuroscience | volume = 417 | pages = 1–10 | date = October 2019 | pmid = 31400490 | doi = 10.1016/j.neuroscience.2019.07.046 | s2cid = 199527439 }}</ref> It is found that [[Endocannabinoid system|endocannabinoid]] signaling mediates oxytocin-driven social reward.<ref>{{cite journal | vauthors = Wei D, Lee D, Cox CD, Karsten CA, Peñagarikano O, Geschwind DH, Gall CM, Piomelli D | title = Endocannabinoid signaling mediates oxytocin-driven social reward | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 45 | pages = 14084–14089 | date = November 2015 | pmid = 26504214 | pmc = 4653148 | doi = 10.1073/pnas.1509795112 | doi-access = free | bibcode = 2015PNAS..11214084W }}</ref> During a 2008 study, a lack of oxytocin in mice was associated with abnormalities in emotional behavior.<ref>{{cite journal | vauthors = Lerer E, Levi S, Salomon S, Darvasi A, Yirmiya N, Ebstein RP | title = Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition | journal = Molecular Psychiatry | volume = 13 | issue = 10 | pages = 980–988 | date = October 2008 | pmid = 17893705 | doi = 10.1038/sj.mp.4002087 | s2cid = 19513481 | doi-access = free }}</ref> Another study conducted in 2014 saw similar results with a variation in the oxytocin receptor connected with dopamine transport and how levels of oxytocin are dependent on the levels of dopamine transporter levels.<ref>{{cite journal | vauthors = Chang WH, Lee IH, Chen KC, Chi MH, Chiu NT, Yao WJ, Lu RB, Yang YK, Chen PS | title = Oxytocin receptor gene rs53576 polymorphism modulates oxytocin-dopamine interaction and neuroticism traits--a SPECT study | journal = Psychoneuroendocrinology | volume = 47 | pages = 212–220 | date = September 2014 | pmid = 25001970 | doi = 10.1016/j.psyneuen.2014.05.020 | s2cid = 22163043 }}</ref>

==Chemistry==
[[File:Oxytocin-neurophysin.png|thumb|Oxytocin (ball-and-stick) bound to its carrier protein neurophysin (ribbons)]]

Oxytocin is a [[peptide]] of nine [[amino acid]]s (a [[nonapeptide]]) in the sequence cysteine-tyrosine-isoleucine-glutamine-asparagine-cysteine-proline-leucine-glycine-amide ([[cysteine|Cys]]&nbsp;–&nbsp;[[tyrosine|Tyr]]&nbsp;–&nbsp;[[isoleucine|Ile]]&nbsp;–&nbsp;[[glutamine|Gln]]&nbsp;–&nbsp;[[asparagine|Asn]]&nbsp;–&nbsp;Cys&nbsp;–&nbsp;[[proline|Pro]]&nbsp;–&nbsp;[[leucine|Leu]]&nbsp;–&nbsp;[[glycine|Gly]]&nbsp;–&nbsp;NH<sub>2</sub>, or CYIQNCPLG-NH<sub>2</sub>); its ''C''-terminus has been converted to a [[primary amide]] and a [[disulfide bridge]] joins the cysteine [[moiety (chemistry)|moieties]].<ref name = OxytocinVasopressinStructures>{{cite book | url = https://books.google.com/books?id=BBLRUI4aHhkC&q=vasopressin+oxytocin+amino+acid+sequence&pg=PA1833 | page = 1833 | title = Tietz Textbook of Clinical Chemistry and Molecular Diagnostics| vauthors = Burtis CA, Ashwood ER, Bruns DE |publisher = [[Elsevier Health Sciences]]|year = 2012|isbn = 978-1-4557-5942-2|edition = 5th}}</ref> Oxytocin has a [[molecular mass]] of 1007&nbsp;[[dalton (unit)|Da]], and one [[international unit]] (IU) of oxytocin is the equivalent of 1.68&nbsp;[[microgram|μg]] of pure peptide.<ref>{{cite web|url=https://www.nibsc.org/documents/ifu/76-575.pdf|title=WHO International Standard OXYTOCIN 4th International Standard NIBSC code: 76/575: Instructions for use (Version 4.0, Dated 30/04/2013)|website=Nibsc.org|access-date=5 March 2022}}</ref>

While the structure of oxytocin is highly conserved in placental mammals, a novel structure of oxytocin was reported in 2011 in [[marmoset]]s, [[tamarin]]s, and other new world [[primates]]. Genomic sequencing of the gene for oxytocin revealed a single [[In-frame mutation#in-frame|in-frame mutation]] ([[thymine]] for [[cytosine]]) which results in a single amino acid substitution at the 8-position ([[proline]] for [[leucine]]).<ref name= "pmid21411453">{{cite journal | vauthors = Lee AG, Cool DR, Grunwald WC, Neal DE, Buckmaster CL, Cheng MY, Hyde SA, Lyons DM, Parker KJ | title = A novel form of oxytocin in New World monkeys | journal = Biology Letters | volume = 7 | issue = 4 | pages = 584–587 | date = August 2011 | pmid = 21411453 | pmc = 3130245 | doi = 10.1098/rsbl.2011.0107 }}</ref> Since this original Lee ''et al.'' paper, two other laboratories have confirmed Pro8-OT and documented additional oxytocin structural variants in this primate taxon. Vargas-Pinilla ''et al.'' sequenced the coding regions of the OXT gene in other genera in new world primates and identified the following variants in addition to Leu8- and Pro8-OT: Ala8-OT, Thr8-OT, and Val3/Pro8-OT.<ref>{{cite journal | vauthors = Vargas-Pinilla P, Paixão-Côrtes VR, Paré P, Tovo-Rodrigues L, Vieira CM, Xavier A, Comas D, Pissinatti A, Sinigaglia M, Rigo MM, Vieira GF, Lucion AB, Salzano FM, Bortolini MC | title = Evolutionary pattern in the OXT-OXTR system in primates: coevolution and positive selection footprints | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 1 | pages = 88–93 | date = January 2015 | pmid = 25535371 | pmc = 4291646 | doi = 10.1073/pnas.1419399112 | doi-access = free | bibcode = 2015PNAS..112...88V }}</ref> Ren ''et al.'' identified a  variant further, Phe2-OT in [[howler monkey]]s.<ref>{{cite journal | vauthors = Ren D, Lu G, Moriyama H, Mustoe AC, Harrison EB, French JA | title = Genetic diversity in oxytocin ligands and receptors in New World monkeys | journal = PLOS ONE | volume = 10 | issue = 5 | article-number = e0125775 | date = 2015 | pmid = 25938568 | pmc = 4418824 | doi = 10.1371/journal.pone.0125775 | doi-access = free | bibcode = 2015PLoSO..1025775R }}</ref>

Recent advances in analytical instrumental techniques highlighted the importance of liquid chromatography (LC) coupled with mass spectrometry (MS) for measuring oxytocin levels in various samples derived from biological sources. Most of these studies optimized the oxytocin quantification in electrospray ionization (ESI) positive mode, using [M+H]<sup>+</sup> as the parent ion at mass-to-charge ratio (''m/z'') 1007.4 and the fragment ions as diagnostic peaks at ''m/z'' 991.0,<ref>{{Cite journal| vauthors = Moriyama E, Kataoka H |date=2015-06-30|title=Automated Analysis of Oxytocin by On-Line in-Tube Solid-Phase Microextraction Coupled with Liquid Chromatography-Tandem Mass Spectrometry|journal=Chromatography|language=en|volume=2|issue=3|pages=382–391|doi=10.3390/chromatography2030382|issn=2227-9075|doi-access=free}}</ref> ''m/z'' 723.2<ref>{{cite journal | vauthors = Wang L, Marti DW, Anderson RE | title = Development and Validation of a Simple LC-MS Method for the Quantification of Oxytocin in Dog Saliva | journal = Molecules | volume = 24 | issue = 17 | page = 3079 | date = August 2019 | pmid = 31450590 | pmc = 6749683 | doi = 10.3390/molecules24173079 | doi-access = free }}</ref> and ''m/z'' 504.2.<ref>{{cite journal | vauthors = Franke AA, Li X, Menden A, Lee MR, Lai JF | title = Oxytocin analysis from human serum, urine, and saliva by orbitrap liquid chromatography-mass spectrometry | journal = Drug Testing and Analysis | volume = 11 | issue = 1 | pages = 119–128 | date = January 2019 | pmid = 30091853 | pmc = 6349498 | doi = 10.1002/dta.2475 }}</ref> These important ion selections paved the way for the development of current methods of oxytocin quantification using MS instrumentation.

The structure of oxytocin is very similar to that of vasopressin.  Both are nonapeptides with a single disulfide bridge, differing only by two substitutions in the amino acid sequence (differences from oxytocin bolded for clarity): Cys&nbsp;–&nbsp;Tyr&nbsp;–&nbsp;'''[[phenylalanine|Phe]]'''&nbsp;–&nbsp;Gln&nbsp;–&nbsp;Asn&nbsp;–&nbsp;Cys&nbsp;–&nbsp;Pro&nbsp;–&nbsp;'''[[arginine|Arg]]'''&nbsp;–&nbsp;Gly&nbsp;–&nbsp;NH<sub>2</sub>.<ref name="OxytocinVasopressinStructures" /> Oxytocin and vasopressin were isolated and their [[total synthesis]] reported in 1954,<ref>{{cite journal|title = The Synthesis of Oxytocin| vauthors = Du Vigneaud V, Ressler C, Swan JM, Roberts CW, Katsoyannis PG |journal = [[Journal of the American Chemical Society]]|volume = 76|issue = 12|pages = 3115–21|year = 1954|doi = 10.1021/ja01641a004| bibcode = 1954JAChS..76.3115D }}</ref> work for which [[Vincent du Vigneaud]] was awarded the 1955 [[Nobel Prize in Chemistry]] with the citation: "for his work on biochemically important sulphur compounds, especially for the first synthesis of a polypeptide hormone."<ref>{{cite web|title = The Nobel Prize in Chemistry 1955|website = Nobelprize.org|url = http://nobelprize.org/nobel_prizes/chemistry/laureates/1955/index.html|access-date = 17 November 2016|publisher = [[Nobel Media AB]]}}</ref>

Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides, including corticotropin-releasing hormone and dynorphin, for example, that act locally. The [[magnocellular neurosecretory cell]]s that make oxytocin are adjacent to magnocellular neurosecretory cells that make vasopressin. These are large neuroendocrine neurons which are excitable and can generate action potentials.<ref name="pmid10221785">{{cite journal | vauthors = Leng G, Brown CH, Russell JA | title = Physiological pathways regulating the activity of magnocellular neurosecretory cells | journal = Progress in Neurobiology | volume = 57 | issue = 6 | pages = 625–655 | date = April 1999 | pmid = 10221785 | doi = 10.1016/s0301-0082(98)00072-0 | s2cid = 240663 }}</ref>

==In medicine==
[[Small-molecule]] [[oxytocin receptor agonist]]s like [[LIT-001]] may prove to be useful in the treatment of [[social disorder|social deficit]]s, for instance in [[autism]].<ref name="pmid34550574">{{cite book | vauthors = Nashar PE, Whitfield AA, Mikusek J, Reekie TA | title = Oxytocin | chapter = The Current Status of Drug Discovery for the Oxytocin Receptor | series = Methods Mol Biol | volume = 2384 | pages = 153–174 | date = 2022 | publisher = Springer | location = New York, NY | pmid = 34550574 | doi = 10.1007/978-1-0716-1759-5_10 | isbn = 978-1-0716-1758-8 | s2cid = 239090096 | chapter-url = }}</ref><ref name="pmid30509888">{{cite journal | vauthors = Gulliver D, Werry E, Reekie TA, Katte TA, Jorgensen W, Kassiou M | title = Targeting the Oxytocin System: New Pharmacotherapeutic Approaches | journal = Trends Pharmacol Sci | volume = 40 | issue = 1 | pages = 22–37 | date = January 2019 | pmid = 30509888 | doi = 10.1016/j.tips.2018.11.001 | s2cid = 54559394 | url = https://unsworks.unsw.edu.au/bitstreams/547ad575-bc60-4b4e-8bd3-681eff7ee47e/download| hdl = 1959.4/unsworks_81554 | hdl-access = free }}</ref><ref name="pmid30199637">{{cite journal | vauthors = Frantz MC, Pellissier LP, Pflimlin E, Loison S, Gandía J, Marsol C, Durroux T, Mouillac B, Becker JA, Le Merrer J, Valencia C, Villa P, Bonnet D, Hibert M | title = LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism | journal = J Med Chem | volume = 61 | issue = 19 | pages = 8670–8692 | date = October 2018 | pmid = 30199637 | doi = 10.1021/acs.jmedchem.8b00697 | s2cid = 52181935 | url = https://hal.science/hal-02366272/file/acs.jmedchem.8b00697.pdf}}</ref>

== See also ==
* [[Oxytocin (medication)]]

== References ==
{{Reflist}}

== Further reading ==
{{Refbegin}}
* {{cite book | chapter-url = http://refworks.springer.com/mrw/fileadmin/pdf/Neurochemistry/0387303480C25.PDF | title = Handbook of neurochemistry and molecular neurobiology | publisher = Springer | year = 2006 | isbn = 978-0-387-30348-2 | location = Berlin | pages = 573–607 | chapter = Oxytocin and Vasopressin: Genetics and Behavioral Implications | vauthors = Caldwell HK, Young WS | veditors = Abel L, Lim R | archive-date = 2011-05-04 | access-date = 2006-05-24 | archive-url = https://web.archive.org/web/20110504131252/http://refworks.springer.com/mrw/fileadmin/pdf/Neurochemistry/0387303480C25.PDF }}
* {{cite book | contribution = Oxytocin as proximal cause of 'maternal instinct': weak science, post-feminism, and the hormones of mystique | veditors = Schmitz S, Höppner G | title = Gendered neurocultures: feminist and queer perspectives on current brain discourses| publisher = Zaglossus | location = Wien | year = 2014 | isbn = 978-3-902902-12-2 | series = challenge GENDER, 2 }}
* {{cite magazine | title= The weak science behind the wrongly named moral molecule | date= 13 November 2015 | url= https://www.theatlantic.com/science/archive/2015/11/the-weak-science-of-the-wrongly-named-moral-molecule/415581/ | vauthors= Yong E | author1-link= Ed Yong | magazine= [[The Atlantic]] }}.
{{Refend}}

== External links ==
* {{Commons category-inline}}

{{Women's health|state=collapsed}}
{{Hormones}}
{{Neuropeptides}}
{{Neurotransmitters}}
{{Galactagogues}}
{{Oxytocin and vasopressin receptor modulators}}
{{Opioid receptor modulators}}
{{Authority control}}

[[Category:Analgesics]]
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[[Category:Gynaecological endocrinology]]
[[Category:Hormones of the hypothalamus]]
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[[Category:Human female endocrine system]]
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[[Category:Neuropeptides]]
[[Category:Neurotransmitters]]
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[[Category:Oxytocin receptor agonists]]
[[Category:Posterior pituitary hormones]]
[[Category:Vasopressin receptor agonists]]
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[[Category:Nonapeptides]]
[[Category:Happy hormones]]