Oxytocin and Oxytocin (medication): Difference between pages

{{distinguish|Oxycontin}}

{{Drugbox

| Verifiedfields = changed

| verifiedrevid = 456481037

| 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-hydroxybenzoyl)-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

| width = 250px

<!--Clinical data-->

| pronounce = {{IPAc-en|ˌ|ɒ|k|s|ɨ|ˈ|t|oʊ|s|ɪ|n}}

| tradename = Pitocin

| legal_US = RX

| routes_of_administration = [[Nasal spray|Intranasal]], [[Intravenous therapy|IV]], [[Intramuscular injection|IM]]

<!--Pharmacokinetic data-->

| protein_bound = 30%

| metabolism = hepatic 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 = 1582–6 |date=September 2012 | pmid = 22436536 | doi = 10.1016/j.psyneuen.2012.02.014 | url = http://linkinghub.elsevier.com/retrieve/pii/S0306-4530(12)00069-8}}</ref><ref name="pmid22467107">{{cite journal | vauthors = Huffmeijer R, Alink LR, Tops M, ''et al.'' | title = Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration | journal = Neuro Endocrinol. Lett. | volume = 33 | issue = 1 | pages = 21–5 | year = 2012 | pmid = 22467107 | doi = | url = }}</ref>

| excretion = Biliary and [[Kidney|renal]]

<!--Identifiers-->

| ATC_prefix = H01

| ATC_suffix = BB02

| ChEMBL_Ref = {{ebicite|changed|EBI}}

<!--Chemical data-->

| molecular_weight = 1007.19 g/mol

| 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

| InChI = 1/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

<!-- Definition -->

'''Oxytocin''' ('''Oxt''') is a nonapeptide [[neurohypophysial hormone|hormone]] in [[mammal]]s.&nbsp; It is also available as a medication.<ref name=AHFS2015>{{cite web|title=Oxytocin|url=http://www.drugs.com/monograph/oxytocin.html|publisher=The American Society of Health-System Pharmacists|accessdate=June 2015}}</ref>

<!-- Mechanism of action -->

Oxytocin is normally produced in the [[hypothalamus]]<ref>{{cite journal | vauthors = Barberis C, Mouillac B, Durroux T | title = Structural bases of vasopressin/oxytocin receptor function | journal = The Journal of Endocrinology | volume = 156 | issue = 2 | pages = 223–9 | date = Feb 1998 | pmid = 9518866 }}</ref> and stored in the [[posterior pituitary gland]].<ref>{{Cite web|title = OXYTOCIN {{!}} C43H66N12O12S2 - PubChem|url = http://pubchem.ncbi.nlm.nih.gov/compound/oxytocin|website = pubchem.ncbi.nlm.nih.gov|accessdate = 2015-07-25|first = |last = Pubchem}}</ref> It plays a role in [[intimacy]], [[sexual reproduction]] of both sexes, and during and after [[childbirth]] as well as social bonding.<ref>{{cite journal | vauthors = Olff M, Frijling JL, Kubzansky LD, Bradley B, Ellenbogen MA, Cardoso C, Bartz JA, Yee JR, van Zuiden M | title = The role of oxytocin in social bonding, stress regulation and mental health: an update on the moderating effects of context and interindividual differences | journal = Psychoneuroendocrinology | volume = 38 | issue = 9 | pages = 1883–94 | date = Sep 2013 | pmid = 23856187 | doi = 10.1016/j.psyneuen.2013.06.019 }}</ref> It is released in large amounts after distension of the [[cervix]] and [[uterus]] during labor and with stimulation of the nipples following childbirth. This helps with [[childbirth|birth]], [[maternal bonding]], and [[lactation]].<ref>Marieb Human Anatomy & Physiology 9th edition, chapter:16, p. 599</ref> Studies have looked at oxytocin's role in various behaviors, including [[orgasm]], [[social recognition]], [[pair bond]]ing, [[anxiety]], 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 = 127–51 | date = Jun 2009 | pmid = 19482229 | pmc = 2689929 | doi = 10.1016/j.pneurobio.2009.04.001 }}</ref> As a medication, it is used to cause contraction of the [[uterus]], which is used to [[labor induction|start labor]], [[augmentation (obstetrics)|increase the speed of labor]], and to stop [[postpartum bleeding|bleeding following delivery]].<ref name="AHFS2015" />

<!-- Society and culture -->

It is on the [[World Health Organization's List of Essential Medicines]], a list of the most important medications needed in a basic [[health system]].<ref>{{cite web|title=WHO Model List of EssentialMedicines|url=http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1|work=World Health Organization|accessdate=22 April 2014|date=October 2013}}</ref>

{{TOC limit|3}}

==Physiological effects {{anchor|Actions within the brain}}==

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]] that requires [[magnesium]] and [[cholesterol]]. It belongs to the [[rhodopsin]]-type (class I) group of G-protein-coupled receptors.

The peripheral actions of oxytocin mainly reflect secretion from the [[pituitary gland]]. (See [[oxytocin receptor]] for more detail on its action.) Oxytocin secreted from the [[pituitary gland]] cannot re-enter the brain because of the [[blood–brain barrier]].{{citation needed|date=March 2015}} Instead, 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]].

* [[Letdown reflex]]: In [[lactation|lactating]] ([[breastfeeding]]) mothers, oxytocin acts at the [[mammary gland]]s, causing milk to be 'let down' into [[areola|subareolar]] [[sinuses]], 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 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]]. Oxytocin release during breastfeeding causes mild but often painful contractions 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 [[parturition]] 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 = 16096–101 | date = Nov 2005 | pmid = 16249339 | pmc = 1276060 | doi = 10.1073/pnas.0505312102 }}</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 = 224–7 | date = Dec 2004 | pmid = 15677415 | doi = 10.1196/annals.1314.025 }}</ref> and [[wound healing]]: Oxytocin is also thought to modulate [[inflammation]] by decreasing certain [[cytokines]]. 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 = 1082–90 | date = Aug 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>Miho Nakajima, Andreas Görlich and Nathaniel Heintz. Oxytocin Modulates Female Sociosexual Behavior through a Specific Class of Prefrontal Cortical Interneurons. doi:10.1016/j.cell.2014.09.020 Lay summary: http://www.sciguru.org/newsitem/17672/love-hormone-oxycotin-regulates-sociosexual-behavior-female-mice</ref>

* The relationship between oxytocin and human sexual response is unclear. At least two uncontrolled studies have found increases in [[blood plasma|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 = Jan 1987 | pmid = 3782434 | doi = 10.1210/jcem-64-1-27 | url = http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=3782434 }}</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 = Feb 1994 | pmid = 8135652 | doi = 10.1007/BF01541618 }}</ref> Plasma oxytocin levels are notably 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 = 125–6 | year = 1999 | pmid = 9949283 | doi = 10.1159/000010075 }}</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 = 217–21 | year = 1995 | pmid = 8586300 | doi = 10.1159/000292340 }}</ref> Murphy et al. (1987), studying men, found oxytocin levels were raised throughout sexual arousal with no acute increase at orgasm.<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 = 738–41 | date = Oct 1987 | pmid = 3654918 | doi = 10.1210/jcem-65-4-738 | url = http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=3654918 }}</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 = Apr 2003 | pmid = 12697037 | doi = 10.1677/joe.0.1770057 }}</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 | pages = 28 | year = 2006 | pmid = 17034623 | pmc = 1621060 | doi = 10.1186/1745-0179-2-28 }}</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, 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 = Biol. Psychiatry | volume = 54 | issue = 12 | pages = 1389–98 | year = 2003 | pmid = 14675803 | doi = 10.1016/S0006-3223(03)00465-7 }}</ref>

* Due to its similarity to [[vasopressin]], it can reduce the excretion of [[urine]] slightly. In several species, oxytocin can stimulate sodium excretion from the kidneys (natriuresis), and, in humans, high doses can result in [[hyponatremia]].

* 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 = 9550–5 | date = Jul 2002 | pmid = 12093924 | pmc = 123178 | doi = 10.1073/pnas.152302499 }}</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 = 13074–9 | date = Aug 2004 | pmid = 15316117 | pmc = 516519 | doi = 10.1073/pnas.0405324101 }}</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 | pages = | isbn = 83-200-1415-8 }}{{Page needed|date=September 2010}}</ref>

* [[Autism spectrum|Autism]]: Oxytocin may play a role in autism and may be an effective [[Autism therapies#Prescription medication|treatment for autism]]'s repetitive and affiliative behaviors.<ref>{{cite journal | vauthors = Bartz JA, Hollander E | title = Oxytocin and experimental therapeutics in autism spectrum disorders | journal = Progress in Brain Research | volume = 170 | issue = | pages = 451–62 | year = 2008 | pmid = 18655901 | doi = 10.1016/S0079-6123(08)00435-4 | isbn = 978-0-444-53201-5 | series = Progress in Brain Research }}</ref> Oxytocin treatments also resulted in an increased retention of affective speech in adults 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 = Apr 2007 | pmid = 17383819 | pmc = 2705963 | doi = 10.1016/j.neulet.2007.02.001 }}</ref> Two related studies in adults, in 2003 and 2007, found oxytocin decreased repetitive behaviors and improved interpretation of emotions. More recently, intranasal administration of oxytocin was found to increase emotion recognition in children as young as 12 who are diagnosed with autism spectrum disorders.<ref name="Guastella2010">{{cite journal | vauthors = Guastella AJ, Einfeld SL, Gray KM, Rinehart NJ, Tonge BJ, Lambert TJ, Hickie IB | title = Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders | journal = Biological Psychiatry | volume = 67 | issue = 7 | pages = 692–4 | date = Apr 2010 | pmid = 19897177 | doi = 10.1016/j.biopsych.2009.09.020 }}</ref> Oxytocin has also been implicated in the etiology of autism, with one report suggesting autism is correlated with genomic deletion of the gene containing the oxytocin receptor gene ([[Oxytocin receptor|''OXTR'']]). Studies involving Caucasian and Finnish samples and Chinese Han families provide support for the relationship of ''OXTR'' with autism.<ref name="Gregory2009"/><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 = 629–39 | date = Mar 2010 | pmid = 19777562 | doi = 10.1002/ajmg.b.31032 }}</ref> Autism may also be associated with an aberrant methylation of ''OXTR''.<ref name="Gregory2009"/> After treatment with inhaled oxytocin, autistic patients exhibit more appropriate social behavior.<ref name="Andaria_2010">{{cite journal | vauthors = Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A | title = Promoting social behavior with oxytocin in high-functioning autism spectrum disorders | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 9 | pages = 4389–94 | date = Mar 2010 | pmid = 20160081 | pmc = 2840168 | doi = 10.1073/pnas.0910249107 | url = http://www.pnas.org/content/early/2010/02/05/0910249107.abstract | laysummary = http://www.scientificamerican.com/podcast/episode.cfm?id=oxytocin-may-alleviate-some-autism-10-02-16 | laysource = Scientific American }}</ref> While this research suggests some promise, further clinical trials of oxytocin are required to demonstrate potential benefit and side effects in the treatment of autism. As such, researchers do not recommend use of oxytocin as a treatment for autism outside of clinical trials.<ref name="pmid22795645">{{cite journal | vauthors = Gordon I, Vander Wyk BC, Bennett RH, Cordeaux C, Lucas MV, Eilbott JA, Zagoory-Sharon O, Leckman JF, Feldman R, Pelphrey KA | title = Oxytocin enhances brain function in children with autism | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 52 | pages = 20953–8 | date = Dec 2013 | pmid = | doi = 10.1073/pnas.1312857110 | laysummary = http://www.nytimes.com/2013/12/03/health/oxytocin-found-to-stimulate-brain-in-children-with-autism.html?hp&_r=1& | laysource = New York Times }}</ref>

* Increasing [[Trust (sociology)|trust]] and reducing [[fear]]: 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">{{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 = 673–6 | date = Jun 2005 | pmid = 15931222 | doi = 10.1038/nature03701 }}</ref> Nasally administered oxytocin has also 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 = 11489–93 | date = Dec 2005 | pmid = 16339042 | 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 = 245–8 | date = Apr 2005 | pmid = 15821089 | doi = 10.1126/SCIENCE.1105636 }}</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 = 104–7 | date = Jul 2011 | pmid = 21719680 | doi = 10.1126/SCIENCE.1201043 }}</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 = 864–70 | date = Nov 2009 | pmid = 19640508 | doi = 10.1016/j.biopsych.2009.06.009 }}</ref>

* [[Trust (social sciences)|Trust]] is increased by oxytocin.<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 = 128–32 | date = Jun 2009 | pmid = 19344725 | doi = 10.1016/j.yhbeh.2009.03.019 }}</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 = 676–81 | year = 2013 | pmid = 22554106 | doi = 10.1080/00207594.2012.677540 }}</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 = 2800–4 | date = Nov 2013 | pmid = 23768973 | doi = 10.1016/j.psyneuen.2013.05.006 }}</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 = 639–50 | date = May 2008 | pmid = 18498743 | doi = 10.1016/j.neuron.2008.04.009 }}</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" />

* While Oxytocin increases [[Trust (social sciences)|trust]],<ref name="Theodoridou_2009" /><ref name="Lane_2013" /><ref name="Cardoso_2013" /> it does so only to a certain degree. In a study, participants played a variation of the [[trust game]] and acted as an “investor,” deciding how much money to allocate to a “trustee.”<ref name="pmid20631321">{{cite journal | vauthors = Mikolajczak M, Gross JJ, Lane A, Corneille O, de Timary P, Luminet O | title = Oxytocin makes people trusting, not gullible | journal = Psychological Science | volume = 21 | issue = 8 | pages = 1072–4 | date = Aug 2010 | pmid = 20631321 | doi = 10.1177/0956797610377343 }}</ref> The trustee was described as trustworthy, untrustworthy, or neutral. Participants who received [[intranasal]] oxytocin gave more money to the trustworthy and neutral trustees. Participants that received oxytocin did not give more money to the untrustworthy trustee, implying that oxytocin only increases trust when there is no reason to be distrustful.<ref name="Cardoso_2013" /> 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]] 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 = 810–6 | date = Jun 2014 | pmid = 23547247 | doi = 10.1093/scan/nst042 }}</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 = 16074–9 | date = Nov 2012 | pmid = 23152592 | 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 = 1262–6 | date = Jan 2011 | pmid = 21220339 | pmc = 3029708 | doi = 10.1073/pnas.1015316108 }}</ref> Furthermore, genetic differences in the [[oxytocin receptor]] gene (OXTR) have been associated with maladaptive social traits such as aggressive behaviour.<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 = 545–51 | date = Jul 2012 | pmid = 22372486 | doi = 10.1111/j.1601-183X.2012.00776.x }}</ref>

* 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 | pages = e1128 | year = 2007 | pmid = 17987115 | pmc = 2040517 | doi = 10.1371/journal.pone.0001128 | editor1-last = Brosnan | editor1-first = Sarah }}</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=160–166 |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 = Apr 2010 | pmid = 20371820 | 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 = 731–3 | date = Mar 2007 | pmid = 17137561 | doi = 10.1016/j.biopsych.2006.07.015 }}</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 = Jan 2008 | pmid = 17888410 | doi = 10.1016/j.biopsych.2007.06.026 }}</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 = 781–91 | date = Dec 2008 | pmid = 19102589 | pmc = 2672051 | doi = 10.1037/a0014195 }}</ref>

* Cognitive function: Certain learning and memory functions are impaired by centrally administered oxytocin.<ref name="Gimpl" /> Also, systemic oxytocin administration can impair memory retrieval in certain aversive memory tasks.<ref name="pmid16997585">{{cite journal | vauthors = de Oliveira LF, Camboim C, Diehl F, Consiglio AR, Quillfeldt JA | title = Glucocorticoid-mediated effects of systemic oxytocin upon memory retrieval | journal = Neurobiology of Learning and Memory | volume = 87 | issue = 1 | pages = 67–71 | date = Jan 2007 | pmid = 16997585 | doi = 10.1016/j.nlm.2006.05.006 }}</ref> Interestingly, oxytocin does seem to facilitate learning and memory specifically for social information. Healthy males administered intranasal oxytocin show improved memory for human faces, in particular happy faces.<ref name="Guastella2008">{{cite journal | vauthors = Guastella AJ, Mitchell PB, Mathews F | title = Oxytocin enhances the encoding of positive social memories in humans | journal = Biological Psychiatry | volume = 64 | issue = 3 | pages = 256–8 | date = Aug 2008 | pmid = 18343353 | doi = 10.1016/j.biopsych.2008.02.008 }}</ref><ref name="Rimelle2009">{{cite journal | vauthors = Rimmele U, Hediger K, Heinrichs M, Klaver P | title = Oxytocin makes a face in memory familiar | journal = The Journal of Neuroscience | volume = 29 | issue = 1 | pages = 38–42 | date = Jan 2009 | pmid = 19129382 | doi = 10.1523/JNEUROSCI.4260-08.2009 }}</ref> They also show improved recognition for positive social cues over threatening social cues <ref name="Unkelbach2008">{{cite journal | vauthors = Unkelbach C, Guastella AJ, Forgas JP | title = Oxytocin selectively facilitates recognition of positive sex and relationship words | journal = Psychological Science | volume = 19 | issue = 11 | pages = 1092–4 | date = Nov 2008 | pmid = 19076479 | doi = 10.1111/j.1467-9280.2008.02206.x }}</ref><ref name="Marsh2010">{{cite journal | vauthors = Marsh AA, Yu HH, Pine DS, Blair RJ | title = Oxytocin improves specific recognition of positive facial expressions | journal = Psychopharmacology | volume = 209 | issue = 3 | pages = 225–32 | date = Apr 2010 | pmid = 20186397 | doi = 10.1007/s00213-010-1780-4 }}</ref> and improved recognition of fear.<ref name="pmid19747930"/>

* Sexual arousal: Oxytocin injected into the [[cerebrospinal fluid]] causes spontaneous [[erection]]s in rats,<ref name="Gimpl">{{cite journal | vauthors = Gimpl G, Fahrenholz F | title = The oxytocin receptor system: structure, function, and regulation | journal = Physiological Reviews | volume = 81 | issue = 2 | pages = 629–83 | date = Apr 2001 | pmid = 11274341 | url = http://physrev.physiology.org/cgi/pmidlookup?view=long&pmid=11274341 }}</ref> reflecting actions in the hypothalamus and spinal cord. Centrally administrated oxytocin receptor antagonists can prevent noncontact erections, which is a measure of sexual arousal. Studies using oxytocin antagonists in female rats provide data that oxytocin increases [[lordosis behavior]], indicating an increase in sexual receptivity.<ref name="Bancroft2005">{{cite journal | vauthors = Bancroft J | title = The endocrinology of sexual arousal | journal = The Journal of Endocrinology | volume = 186 | issue = 3 | pages = 411–27 | date = Sep 2005 | pmid = 16135662 | doi = 10.1677/joe.1.06233 }}</ref>

* Bonding: In the [[prairie vole]], oxytocin released into the brain of the female during sexual activity is important for forming a monogamous pair bond with her sexual partner. Vasopressin appears to have a similar effect in males.<ref>[http://www.americanscientist.org/issues/pub/high-on-fidelity Vacek M, High on Fidelity. What can voles teach us about monogamy? ]</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 five to 24 minutes of a petting session. This possibly plays a role in the [[human-canine bond|emotional bonding between humans and dogs]].<ref>[http://books.google.com/books?hl=en&lr=&id=VO6dp52RxnQC&oi=fnd&pg=PR5&dq=oxytocin+petting+dog&ots=mTRRd4zj_9&sig=5xIdHdfrvmOOmZJh0Eak_KgYl2w#v=onepage&q=%20petting%20dog&f=false Kuchinskas Susan, The Chemistry of Connection: How the Oxytocin Response Can Help You Find Trust, Intimacy, and Love p65]</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 = 275–82 | date = Feb 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 web |url=http://neuroendo.org.uk/index.php/content/view/34/11/ |title=The Neurobiology of Social Bonds |author=Kendrick KM |date=2004-01-01 |publisher=British Society for Neuroendocrinology |accessdate=2009-04-13}}</ref> Oxytocin is involved in the initiation of 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 = Jan 2010 | pmid = 20953313 | pmc = 2953948 | doi = 10.1002/dev.20411 }}</ref>

* Drug interactions: According to some studies in animals, oxytocin inhibits the development of 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 = 945–62 | date = Nov 1998 | pmid = 9924746 | doi = 10.1016/S0306-4530(98)00064-X }}</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 = 509–14 | date = May 2007 | pmid = 17383105 | doi = 10.1016/j.neuroscience.2007.02.032 }}</ref> The [[anxiolytic]] [[Buspar]] (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 = 1635–40 | year = 1996 | pmid = 9025112 | doi = 10.1016/S0028-3908(96)00078-0 }}</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 = 187–92 | date = Apr 1996 | pmid = 8771561 | doi = 10.1016/S0143-4179(96)90086-4 }}</ref>

* Preparing fetal neurons for delivery: 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 = 1788–92 | date = Dec 2006 | pmid = 17170309 | doi = 10.1126/science.1133212 }}</ref>

* 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 decreasing their feelings of anxiety when they are separated.<ref name="pmid17034623"/>

*Feeding: Recent evidence has 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 are 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 = 172–7 | date = Aug 2012 | pmid = 22801496 | doi = 10.1038/nature11270 }}</ref>

*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 = 5503–7 | date = Apr 2014 | pmid = 24706799 | doi = 10.1073/pnas.1400724111 | laydate = 2 April 2014 | layurl = http://www.bbc.com/news/science-environment-26771703 | laysource = BBC News }}</ref>

*Oxytocin and intergroup bonding: Oxytocin can increase positive attitudes, such as bonding, toward individuals with similar characteristics, who then become classified as “in-group” members, whereas individuals who are dissimilar become classified as “out-group” members. Race can be used as an example of in-group and out-group tendencies because society often categorizes individuals into groups based on race (Caucasian, African American, Latino, etc.). One study that examined race and empathy found that participants receiving nasally administered oxytocin had stronger reactions to pictures of in-group members making pained faces than to pictures of out-group members with the same expression.<ref name="pmid23246533">{{cite journal | vauthors = Sheng F, Liu Y, Zhou B, Zhou W, Han S | title = Oxytocin modulates the racial bias in neural responses to others' suffering | journal = Biol Psychol | volume = 92 | issue = 2 | pages = 380–6 | year = 2013 | pmid = 23246533 | doi = 10.1016/j.biopsycho.2012.11.018 }}</ref> This shows that oxytocin may be implicated in our ability to empathize with individuals of different races and could potentially translate into willingness to help individuals in pain or stressful situations. Moreover, individuals of one race may be more inclined to help individuals of the same race than individuals of another race when they are experiencing pain. Oxytocin has also been implicated in 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 = 5503–7 | date = Apr 2014 | pmid = 24706799 | doi = 10.1073/pnas.1400724111 }}</ref> Both of these examples show the tendency to act in ways that benefit people with which one feels is part of their social group, or in-group. 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 | pages = e46751 | year = 2012 | pmid = 23144787 | pmc = 3492361 | doi = 10.1371/journal.pone.0046751 }}</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 = 1288–92 | year = 2012 | pmid = 22991128 | doi = 10.1177/0956797612446026 }}</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 = Front Behav Neurosci | volume = 8 | issue = | pages = 266 | year = 2014 | pmid = 25140135 | pmc = 4122242 | doi = 10.3389/fnbeh.2014.00266 }}</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.

===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. Consequently, oxytocin is often referred to as the “love hormone".<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 = 958–60 | date = Sep 2013 | pmid = 23147382 | pmc = 3930442 | doi = 10.1038/mp.2012.156 }}</ref> 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 = 1185–7 | date = Sep 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 the animal or human 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 | pages = e58113 | year = 2013 | pmid = 23469148 | pmc = 3585234 | doi = 10.1371/journal.pone.0058113 }}</ref>

Individuals who receive an intranasal dose of oxytocin identify facial expressions of disgust faster than individuals who do not receive oxytocin.<ref name="Theodoridou e58113"/> 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 = 179–84 | date = Jan 2010 | pmid = 19747930 | doi = 10.1016/j.neuropsychologia.2009.09.003 }}</ref> Oxytocin modulates fear responses by enhancing the maintenance of social memories. Rats that 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"/>

; Sex differences

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 = 1431–8 | date = Sep 2012 | pmid = 22365820 | doi = 10.1016/j.psyneuen.2012.01.011 }}</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"/>

; Effect in predictable and unpredictable stimuli

Oxytocin increases defensive responding to unpredictable stimuli, but not to predictable stimuli. This result leads to the assumption that oxytocin’s effect is context-dependent. Thus, oxytocin may reinforce prosocial behaviors after an initial bond is formed, but may enhance defensive behaviors to unfamiliar individuals.<ref name="Grillon 958–960"/>

Oxytocin is beneficial because it can either enhance social bonding or promote defensive behaviors depending on the situation.<ref name="Grillon 958–960"/> It would not be adaptive if oxytocin consistently enhanced social approach and other prosocial behaviors, especially in uncertain and potentially dangerous social contexts. Fear and anxiety are typically thought to be maladaptive, as these traits often underlie various [[psychological disorders]]. However, it is important to note that both fear and anxiety responses help to protect an individual. These emotions render environmental cues more important, leading to a greater likelihood the individual or animal will acknowledge the potential threat. Ultimately this process leads to a greater chance of survival.

==Medical uses==

An intravenous infusion of oxytocin is used to [[labor induction|induce labor]] and to support labor in case of slow childbirth. It is unclear whether a high dose is better than a standard dose for labor induction. It has largely replaced [[ergometrine]] as the principal agent to increase uterine tone in acute [[postpartum hemorrhage]]. Oxytocin is also used in [[veterinary medicine]] to facilitate birth and to stimulate milk release. The [[tocolytic]] agent [[atosiban]] (Tractocile) acts as an antagonist of oxytocin receptors; this drug is registered in many countries to suppress premature labor between 24 and 33 weeks of gestation. It has fewer side effects than drugs previously used for this purpose ([[ritodrine]], [[salbutamol]], and [[terbutaline]]).<ref>{{cite journal | vauthors = Budden A, Chen LJ, Henry A | title = High-dose versus low-dose oxytocin infusion regimens for induction of labour at term | journal = The Cochrane Database of Systematic Reviews | volume = 10 | pages = CD009701 | date = Oct 9, 2014 | pmid = 25300173 | doi = 10.1002/14651858.CD009701.pub2 }}</ref>

===Side effects===

Oxytocin is relatively safe when used at recommended doses, and side effects are uncommon.<ref name="rxlist">{{Cite web|url= http://www.rxlist.com/pitocin-drug.htm |title= Pitocin (drug label for professionals) |publisher= WebMD |work= Rx List |accessdate=2010-09-09}}</ref> The following maternal [[adverse drug reaction|events]] have been reported:<ref name="rxlist"/>

* [[Tachycardia|Increased heart rate]]

* [[hypotension|Decreased blood pressure]]

* [[Cardiac arrhythmia]] and [[premature ventricular contraction]]

* Impaired uterine blood flow

* [[Fibrinogen#Fibrinogen deficiency|Afibrinogenemia]]

* [[Anaphylaxis]]

Excessive dosage or long-term administration (over a period of 24 hours or longer) have been known to result in [[Tetanic contraction|tetanic]] uterine contractions, [[uterine rupture]], postpartum hemorrhage, and [[water intoxication]], sometimes fatal.

During pregnancy, increased uterine motility has led to [[Bradycardia|decreased heart rate]], cardiac arrhythmia, seizures, [[brain damage]], death in the fetus/neonate:<ref name="rxlist"/>

==Mechanism of action==

Oxytocin is destroyed in the [[gastrointestinal tract]], so it must be administered by injection or as [[nasal spray]]. It has a [[half-life]] of typically about three minutes in the blood when given [[Intravenous therapy|intravenously]]. When administered intranasally via a nasal spray, oxytocin crosses the [[blood–brain barrier]] and exhibits psychoactive effects in humans.<ref name="Oxy BBB">{{cite book | vauthors = Malenka RC, Nestler EJ, Hyman SE | veditors = Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | page = 195 | edition = 2nd | chapter = Chapter 7: Neuropeptides | quote= Oxytocin can be delivered to humans via nasal spray following which it crosses the blood–brain barrier.&nbsp;... In a double-blind experiment, oxytocin spray increased trusting behavior compared to a placebo spray in a monetary game with real money at stake.}}</ref><ref name="Oxytocinergic circuit">{{cite journal | vauthors = McGregor IS, Callaghan PD, Hunt GE | title = From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use? | journal = British Journal of Pharmacology | volume = 154 | issue = 2 | pages = 358–68 | date = May 2008 | pmid = 18475254 | pmc = 2442436 | doi = 10.1038/bjp.2008.132 | quote = Recent studies also highlight remarkable anxiolytic and prosocial effects of intranasally administered OT in humans, including increased ‘trust’, decreased amygdala activation towards fear-inducing stimuli, improved recognition of social cues and increased gaze directed towards the eye regions of others (Kirsch et al., 2005; Kosfeld et al., 2005; Domes et al., 2006; Guastella et al., 2008). }}</ref> Unlike the case of intravenous administration, intranasal oxytocin has a duration of at least 2.25 hours and as long as 4 hours.<ref name="pmid22436536" /><ref name="pmid22467107" />

==Structure==

[[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]]). Its systematic name is cysteine-tyrosine-isoleucine-glutamine-asparagine-cysteine-proline-leucine-glycine-amide ([[cysteine|cys]] – [[tyrosine|tyr]] – [[isoleucine|ile]] – [[glutamine|gln]] – [[asparagine|asn]] – [[cysteine|cys]] – [[proline|pro]] – [[leucine|leu]] – [[glycine|gly]] – NH₂, or CYIQNCPLG-NH₂). Oxytocin has a [[molecular mass]] of 1007 [[dalton (unit)|dalton]]s. One [[international unit]] (IU) of oxytocin is the equivalent of about 2 [[microgram]]s of pure peptide. While the structure of oxytocin is highly conserved in placental mammals, a novel structure of oxytocin was recently reported 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 = 584–7 | date = Aug 2011 | pmid = 21411453 | pmc = 3130245 | doi = 10.1098/rsbl.2011.0107 }}</ref>

The biologically active form of oxytocin, commonly measured by [[Radioimmunoassay|RIA]] and/or [[High-performance liquid chromatography|HPLC]] techniques, is also known as the octapeptide "oxytocin disulfide" (oxidized form), but oxytocin also exists as a reduced dithiol nonapeptide called oxytoceine.<ref>{{Cite journal| author = du Vigneaud V. | title = Experiences in the Polypeptide Field: Insulin to Oxytocin | journal = Annals of the New York Academy of Sciences | volume = 88 | issue = 3 | pages = 537–48 | year = 1960 | pmid = | doi = 10.1111/j.1749-6632.1960.tb20052.x | url = http://www3.interscience.wiley.com/journal/119764459/abstract }}</ref> It has been theorized that open chain oxytoceine (the reduced form of oxytocin) may also act as a [[free radical]] scavenger (by donating an electron to a free radical); oxytoceine may then be oxidized back to oxytocin via the [[dehydroascorbate]] <---> [[ascorbate]] redox couple.<ref name="DLA: Mechanisms by which hypoxia augments Leydig cell viability and differentiated cell function in vitro">{{Cite web| url=http://scholar.lib.vt.edu/theses/available/etd-06062008-170416 | title=Mechanisms by which hypoxia augments Leydig cell viability and differentiated cell function in vitro | author = Kukucka MA | date=1993-04-18 | publisher=Digital Library and Archives | accessdate=2010-02-21}}</ref>

The structure of oxytocin is very similar to that of [[vasopressin]] (cys – tyr – <u>[[phenylalanine|phe]]</u> – gln – asn – cys – pro – <u>[[arginine|arg]]</u> – gly – NH₂), also a nonapeptide with a sulfur bridge, whose sequence differs from oxytocin by two amino acids. A table showing the sequences of members of the vasopressin/oxytocin superfamily and the species expressing them is present in the [[vasopressin]] article. Oxytocin and vasopressin were isolated and synthesized by [[Vincent du Vigneaud]] in 1953, work for which he received the [[Nobel Prize in Chemistry]] in 1955.

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.

==Synthesis, storage, release, and metabolism==

{{PBB|geneid=5020}}

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 = 10236–41 | date = Aug 1985 | pmid = 2991279 | doi = }}</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 = 752–7 | date = Mar 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 = 947–50 | date = Jun 1990 | pmid = 1978246 | doi = 10.1210/mend-4-6-947 }}</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 = 373–8 | date = Jan 1980 | pmid = 6153132 | doi = 10.1126/science.6153132 }}</ref> The inactive precursor protein is progressively 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 = 313–22 | date = Jul 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 = 423–30 | date = Sep 1987 | pmid = 3668432 | doi = 10.1677/joe.0.1140423 }}</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 = | pages = 103–18 | date = Sep 1975 | pmid = 1106295 | doi = 10.1111/j.1749-6632.1975.tb29271.x }}</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 = Biochim. Biophys. Acta | volume = 1751 | issue = 1 | pages = 9–18 | year = 2005 | pmid = 16054015 | doi = 10.1016/j.bbapap.2004.09.011 | url = }}</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 = Biochim. Biophys. Acta | volume = 1751 | issue = 1 | pages = 19–25 | year = 2005 | pmid = 15894523 | doi = 10.1016/j.bbapap.2005.04.006 | url = }}</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 Endocrinol. | volume = 127 | issue = 1 | pages = 76–80 | year = 1992 | pmid = 1355623 | doi = | url = }}</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="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 = 535–9 | year = 1984 | pmid = 6540873 | doi = | url = }}</ref><ref name="pmid1355623" /><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 = 1119–25 | year = 1991 | pmid = 1800950 | doi = | url = }}</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 = Biol. Pharm. Bull. | volume = 20 | issue = 1 | pages = 20–4 | year = 1997 | pmid = 9013800 | doi = | url = }}</ref>

===Neural sources===

In the [[hypothalamus]], oxytocin is made in [[magnocellular neurosecretory cell]]s of the [[supraoptic nucleus|supraoptic]] and [[paraventricular nucleus|paraventricular]] nuclei, 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 oxytocin receptors in the [[nucleus accumbens]].<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 = Sep 2009 | pmid = 19482070 | pmc = 2744157 | doi = 10.1016/j.neuroscience.2009.05.055 }}</ref> The peripheral hormonal and behavioral brain effects of oxytocin are thought to be coordinated through its common release through these collaterals.<ref name="Ross"/> Oxytocin is also made 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 = 150–76 | year = 2004 | pmid = 15589267 | doi = 10.1016/j.yfrne.2004.05.001 }}</ref> Depending on the species, oxytocin receptor-expressing cells are located in other areas, including the [[amygdala]] and [[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 [[axon]]s 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===

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 = 225–7 | date = May 1982 | pmid = 7078636 | doi = 10.1038/297225a0 }}</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 = 410–2 | date = Aug 1982 | pmid = 6124806 | doi = 10.1016/S0140-6736(82)90441-X }}</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 = 1544–6 | date = Apr 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 = 485–7 | year = 1985 | pmid = 3995564 | doi = 10.1007/BF00222364 }}</ref> 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 = 509–15 | year = 1983 | pmid = 6647119 | doi = 10.1016/0196-9781(83)90056-6 }}</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 = 688–91 | date = Apr 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 = 508–11 | date = Apr 1986 | pmid = 3961493 | doi = 10.1126/science.3961493 }}</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 = 303–7 | date = Nov 1988 | pmid = 3195625 | doi = 10.1097/00000441-198811000-00003 | url = http://journals.lww.com/amjmedsci/Fulltext/1988/11000/Oxytocin_and_Vasopressin_Are_Present_in_Human_and.3.aspx }}</ref> The finding of significant amounts of this classically "neurohypophysial" hormone outside the central nervous system raises many questions regarding its possible importance in these different tissues.

====Male====

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 exogenous source of vitamin C (ascorbate) 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 = 185–90 | year = 1992 | pmid = 1456839 | doi = 10.3109/01485019208987723 | url = http://informahealthcare.com/doi/abs/10.3109/01485019208987723 }}</ref>

====Female====

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_2α]] to cause regression of the corpus luteum.

===Miscellaneous===

[[Estrogen]] has been found to increase the [[secretion]] of oxytocin as well as the [[gene expression|expression]] of its [[receptor (biochemistry)|receptor]], the [[oxytocin receptor]], in the [[brain]].<ref name="GoldsteinMeston2005">{{cite book | first1 = Irwin | last1 = Goldstein | first2 = Cindy M. | last2 = Meston | first3 = Susan | last3 = Davis | first4 = Abdulmaged | last4 = Traish | name-list-format = vanc | title = Women's Sexual Function and Dysfunction: Study, Diagnosis and Treatment|url=http://books.google.com/books?id=3J7TnwpbZQwC&pg=PA205|date=17 November 2005|publisher=CRC Press|isbn=978-1-84214-263-9|pages=205–}}</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 = 12462–6 | date = Nov 1997 | pmid = 9356472 | pmc = 25001 | doi = 10.1073/pnas.94.23.12462 | url = http://www.pnas.org/cgi/pmidlookup?view=long&pmid=9356472 }}</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="Gimpl" />

==Brand names==

Synthetic oxytocin is sold as proprietary [[medication]] under the trade names Pitocin and Syntocinon, and as [[generic drug|generic]] oxytocin.

== History ==

The word ''oxytocin'' was coined from the term oxytocic. [[Greek language|Greek]] ὀξύς, ''oxys'', and τόκος, ''tokos'', meaning "quick birth")

Its uterine-contracting properties were discovered by British pharmacologist Sir [[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> And its milk ejection property was described by Ott and Scott in 1910<ref>{{cite journal | last1=Ott |first1=I |last2=Scott |first2=JC |title=The Action of Infundibulum upon Mammary Secretion | journal = Proc Soc Exp Biol | year = 1910 | volume = 8 | pages = 48–49 | name-list-format = vanc }}</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 }}</ref>

Oxytocin became the first 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 = 949–57 | date = Dec 1953 | pmid = 13129273 | doi = }}</ref> or synthesized<ref>{{Cite journal| author = 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 | pmid = | doi = 10.1021/ja01115a553 }}</ref><ref name=Ressler_1954>{{cite journal | vauthors = du Vigneaud V, Ressler C, Swan JM, Roberts CW, Katsoyannis PG | title = The synthesis of oxytocin | journal = J. Am. Chem. Soc. |date=June 1954 | volume = 76 | issue = 12 | pages = 3115–3121 | doi = 10.1021/ja01641a004}}</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}}</ref> Vigneaud was awarded the Nobel Prize 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 = 967–74 | date = Jun 1956 | pmid = 13324123 | doi = 10.1126/science.123.3205.967 }}</ref>

==Research==

Oxytocin nasal sprays have been used to stimulate breastfeeding, but the efficacy of this approach is doubtful.<ref name="pmid16223754">{{cite journal | vauthors = Fewtrell MS, Loh KL, Blake A, Ridout DA, Hawdon J | title = Randomised, double blind trial of oxytocin nasal spray in mothers expressing breast milk for preterm infants | journal = Archives of Disease in Childhood. Fetal and Neonatal Edition | volume = 91 | issue = 3 | pages = F169-74 | date = May 2006 | pmid = 16223754 | pmc = 2672698 | doi = 10.1136/adc.2005.081265 }}</ref>

The trust-inducing property of oxytocin might help those with [[social anxiety]] and [[depression (mood)|depression]],<ref name="pmid20371820" /> but with the potential for abuse with [[confidence trick]]s<ref name="pmid18579733">{{cite journal | vauthors = Petrovic P, Kalisch R, Singer T, Dolan RJ | title = Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity | journal = The Journal of Neuroscience | volume = 28 | issue = 26 | pages = 6607–15 | date = Jun 2008 | pmid = 18579733 | pmc = 2647078 | doi = 10.1523/JNEUROSCI.4572-07.2008 }}</ref><ref name="urlTo sniff at danger - Mind Matters -Health And Fitness - smh.com.au">{{Cite news| url = http://www.smh.com.au/news/mind-matters/to-sniff-at-danger/2006/01/12/1136956247384.html | title = To sniff at danger – Mind Matters | author = | date = 2006-01-12 | work = Health And Fitness | publisher = Boston Globe | pages = | archiveurl = | archivedate = | quote = | accessdate = 2009-04-13}}</ref> and military applications.<ref name="pmid19693065">{{cite journal | vauthors = Dando M | title = Biologists napping while work militarized | journal = Nature | volume = 460 | issue = 7258 | pages = 950–1 | date = Aug 2009 | pmid = 19693065 | doi = 10.1038/460950a | laysummary = http://www.reuters.com/article/newsOne/idUSTRE57I4VL20090819 | laysource = Reuters }}</ref> The use of oxytocin in [[Relationship counseling#Novel practices|relationship counseling]] is being investigated, as research has shown the hormone could both enhance trust and improve people's ability to interpret the emotions of others correctly.<ref>Smith, D. [http://www.smh.com.au/news/science/clashing-couples-to-get-a-spray-of-love/2007/05/25/1179601669078.html# Clashing couples to get a spray of love.] ''Sydney Morning Herald'' May 26, 2007.</ref>

A [[nasal spray]] formulation of oxytocin branded Syntocinon is under development by [[Retrophin]] for the treatment of [[lactation deficiency]] and as a novel treatment for [[autism]] and [[schizophrenia]].<ref name="Retrophin2013">{{cite web | author = Retrophin | title = Retrophin Signs U.S. License Agreement for Syntocinon™ Nasal Spray (Oxytocin) |date=December 2013 | url = http://ir.retrophin.com/releasedetail.cfm?releaseid=813544}}</ref> {{As of|2014|10}}, it has reached [[phase III]], [[Phases of clinical research#Phase II|phase II]], and phase II [[clinical trial]]s for these indications, respectively.<ref name="Retrophin2014a">{{cite web | author = Retrophin | title = Retrophin – Pipeline | url = http://www.retrophin.com/content/pipeline/ | accessdate = 2014-10-24}}</ref> In October 2014, Retrophin divested Syntocinon to [[Turing Pharmaceuticals]].<ref name="Retrophin2014b">{{cite web | author = Retrophin | title = Retrophin Announces Divestment of Non-Core Assets to Turing Pharmaceuticals |date=October 2014 | url = http://ir.retrophin.com/releasedetail.cfm?releaseid=875993}}</ref>

== See also ==

* [[Carbetocin]]

* [[Demoxytocin]]

* [[Merotocin]]

* [[TC OT 39]]

* [[Vasotocin]]

* [[WAY-267,464]]

== References ==

{{Reflist|colwidth=32em}}

== Further reading ==

{{Refbegin}}

* {{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 = 127–51 | date = Jun 2009 | pmid = 19482229 | pmc = 2689929 | doi = 10.1016/j.pneurobio.2009.04.001 }}

* {{cite book| vauthors = Caldwell HK, Young WS | authorlink = | veditors = Abel L, Lim R | title = Handbook of neurochemistry and molecular neurobiology | edition = | publisher = Springer | location = Berlin | year = 2006 | origyear = | pages = 573–607 | quote = | isbn = 0-387-30348-0 | oclc = | doi = | url = http://refworks.springer.com/mrw/fileadmin/pdf/Neurochemistry/0387303480C25.PDF | accessdate = | chapter = Oxytocin and Vasopressin: Genetics and Behavioral Implications }}

{{Refend}}

{{Hormones}}

{{Neuropeptidergics}}

[[Category:Neuropeptides]]

[[Category:Obstetric drugs]]

[[Category:Neuroscience]]

[[Category:Neurotransmitters]]

[[Category:Posterior pituitary hormones]]

[[Category:Interpersonal attraction]]

[[Category:Orgasm]]

[[Category:Breastfeeding]]