Oxytocin

SOME TEN YEARS have now passed since a scientific study, published in the journal Nature, demonstrated that participants who had received a dose of oxytocin were more willing to invest money with someone whose honesty could not be guaranteed, than were those who had been given a dose of placebo.

Since that time, oxytocin has been linked to everything from autism, [10][38] to xenophobia [37] ... and of course, to love.



Oxytocin has recently been back in the news (or maybe it never really left) connecting it to weight loss in men, [11] and in "Drunk in Love" articles cautioning about its similarities to alcohol: [12][34] 

"... both have similar effects on Gamma-Amino Butyric acid (GABA) signalling in the prefrontal cortex and limbic areas of the brain." [33] 

And that is all good, research is, of course, a good thing. It's just that newspaper headlines making bold claims, especially when based on the press release of a single study, tend to make me a bit … um … uneasy? 

… Because even if oxytocin is involved in childbirth, breast feeding, social bonding, love, orgasm, facial recognition, self-perception, extroversion, mother-infant bonding, social memory, comfort, et cetera, it seems unlikely that any one chemical could be acting entirely on its own: we are quite complex beings us humans, are we not? 

The waters are murky, indeed. But still, we must dredge, we must ever so cautiously dredge. 

What follows is an overview of some things known, and many things on the path to being known about oxytocin, though in truth I barely scratched the surface. 

THE OXYTOCIN GENE is believed to have originated from the duplication of a pre-existing gene for the neuropeptide vasopressin. [1]

The duplication leading to the separate genes for vasopressin and oxytocin is estimated to have occurred some 435 million years ago, a timeline which would precede its having originated in connection with suckling or live birth. [1]

Like vasopressin, oxytocin is a neuropeptide: It acts both as a hormone and as a brain neurotransmitter. [4]

Synthesized in the hypothalamus (in red), oxytocin is transported to, and released by the pituitary gland, which is located at the base of the brain. [4][5] 






Oxytocin acts on organs in the body and as a chemical messenger in the brain controlling key aspects of the reproductive system including childbirth and lactation, and aspects of human behaviour. [2]

Oxytocin is controlled by a positive feedback mechanism where release of the hormone causes an action which stimulates more of its own release. [2]

In the female body, oxytocin stimulates the uterine muscles to contract during childbirth, and also increases production of prostaglandins which further increases the contractions.  [2]

During breastfeeding, oxytocin promotes the movement of milk into the breast. [2] 

As a medicine, injectable oxytocin is used to help start or continue labor and to control bleeding after delivery. It is also sometimes used to help milk secretion in breast-feeding. [6]

Intranasal administration of oxytocin

• Since the digestive tract quickly degrades the hormone, oxytocin is usually injected into the bloodstream. [17]

• However, since oxytocin cannot pass the blood-brain barrier, nasal sprays have been investigated as an option to transfer the hormone directly to the brain along olfactory nerve cells. [20][21][22]

• Oxytocin has a short half-life in the blood, estimated between about 3–9 min. [19]

• Intranasal oxytocin has a duration of at least 2.25 hours and as long as 4 hours. [23][24]

Oxytocin & Reproduction

Increases in circulating levels of oxytocin have been shown to accompany orgasm in both men and women. [1][7][8]

Using radio-labelled sperm-sized albumin spheres and an intravenous injection of oxytocin, German gynecologist Ludwig Wildt and colleagues demonstrated that oxytocin promotes transport through the womb and oviducts. [1][9]

Oxytocin plays a role in sperm movement and production of testosterone by the testes. [2]

Silencing of oxytocin receptor (OxtrlNs) in the medial prefrontal cortex of female mice results in the loss of social interest in male mice, specifically during the sexually receptive phase of the estrous cycle. (Nakajima et al 2014) [16][17]

Oxytocin and Pair Bonding & Fidelity 

Prairie voles are socially monogamous
and rear their offspring together.

Meadow voles are not monogamous
and only females rear the young.

• When meadow voles are dosed with oxytocin and vasopressin, they adopt the monogamous behaviour of the prairies voles. [41]

• From the Hammock and Young review of literature on the role of vasopressin and oxytocin in modulating social behaviour in prairie voles: [10]

• High levels of oxytocin receptor in the nucleus accumbens and high levels of vasopressin receptor (V1aR) in the ventral pallidum contribute to monogamous social structure in the prairie vole. 

• The distribution pattern of the V1aR is determined in part by a species-specific repetitive element, or ‘microsatellite’, in the 5′ regulatory region of the gene encoding V1aR. 

• This microsatellite is lengthy in the monogamous prairie vol and a very short version in the non-monogamous montane and meadow voles. 

• These species differences in microsatellite sequence are sufficient to change gene expression in cell culture. 

• Microsatellite variation within the prairie vole species itself also modulates gene expression in vitro as well as receptor distribution patterns in vivo, and influences the probability of social approach and bonding behaviour.

• Building on this, Hui Wang and colleagues found direct evidence that in prairie voles, “the act of mating induces permanent chemical modifications in the chromosomes, affecting the expression of genes that regulate sexual and monogamous behaviour. (Wang et al 2013) [40][41]

• The intranasal administration of oxytocin made male subjects perceive their female partner's face as more attractive compared with unfamiliar women but had no effect on the attractiveness of other familiar women. (Scheele et al 2013) [4][13]

• The intranasal administration of oxytocin has been shown to stimulate men in monogamous relationships to keep a much greater distance between themselves and an attractive woman during a first encounter. (Scheele et al 2012). [4][14]

• During couple conflict, oxytocin was found to significantly reduce emotional arousal in women, and increased emotional arousal in men. [15]  (Ditzen et al 2013) 

• In the men, these increases were related to more positive behaviour, whereas there was no such association in women. 

Oxytocin & Autism

In this 2013 study [38] fMRI was used to see differences created by oxytocin in brain responses to social and non-social pictures in 17 children with autism spectrum disorders. 

"... oxytocin temporarily normalized brain regions responsible for the social deficits seen in children with autism." [39]

From the Simons Foundation Autism Research Initiative website / Nicholette Zeliadt (May 14, 2015)

"The hormone oxytocin is proceeding into clinical trials for people with Phelan-McDermid syndrome, researchers revealed yesterday at the 2015 International Meeting for Autism Research (IMFAR) in Salt Lake City, Utah. The news comes exactly one year after oxytocin, which is involved in pair-bonding and trust, was shown to ease social deficits in a rat model of the autism-linked disorder."

From the 2011 review, Modulating social behavior with oxytocin: How does it work? What does it mean? [19]

 “… it may be less captivating, but more accurate, to refrain so far from describing oxytocin effects as targeting the core features of “autism” or “schizophrenia.” Especially, because it may turn out that the best clinical use of intranasal oxytocin is primarily as an effective (and perhaps non-addictive) anti-anxiety medication which may indirectly impact some (important) symptoms of these disorders. In some way, calling oxytocin a schizophrenia drug or an autism drug may be a bit like calling aspirin a heart attack drug. Aspirin may be a very important tool in a cardiologist toolbox, but it acts broadly and is also used for many other purposes.”

 Oxytocin & Emotional Response

• When recounting a negative event, study participants who receive intranasal oxytocin share more emotional details and stories with more emotional significance. [25]

• Oxytocin administration increases the ratings of trustworthiness and attractiveness of male and female targets in raters of both sexes relative to control ratings. [26]

• In this 2010 study, a single dose of oxytocin or a placebo was administered intranasally to 27 healthy male subjects 45 minutes prior to facial recognition task performance. Subjects who received the dose of oxytocin had an improved ability to recognize fear, but not other emotions. [28]

• Studies involving rodents have shown oxytocin can efficiently inhibit fear responses by activating an inhibitory circuit within the amygdala. [17][30][31]

• Intranasal administration of oxytocin has also been shown to increase envy and Schadenfreude. [32]

• Some researchers have argued that oxytocin has a general enhancing effect on all social emotions. [32]

• Investigating two commonly held theories on how oxytocin exerts its effects on social behaviors, this 2013 study found that intranasal oxytocin administration did not enhance approach/avoidance to social stimuli; nor did it exert a stronger effect on social versus non-social stimuli in the context of processing of emotional expressions and scenes. Instead, the data suggested that oxytocin administration increases the salience of certain social stimuli. [29]

Oxytocin & Self-perception

A 2011 Concordia University study found that oxytocin (intranasal), improved self-perception in social situations, amplifying personality traits such as warmth, trust, altruism and openness. [4][18]

Oxytocin & Group-Serving Dishonesty

This 2014 study found participants given oxytocin were more likely to lie for the benefit of the group: [36]

“Compared with participants receiving placebo, participants receiving oxytocin lied more to benefit their groups, did so quicker, and did so without expectation of reciprocal dishonesty from their group members. A control setting ruled out that oxytocin drives self-serving dishonesty.”

Oxytocin & Prader-Willi-syndrome

This  2012 study suggested that oxytocin neurons in the para-ventricular hypothalamus may play a key role in suppressing appetite under normal conditions, and that eating may be triggered 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. [17][35]

Updates / Related

More Doubts Over The Oxytocin And Trust Theory / Discover Magazine / September 16, 2015

***

FIN

REFERENCES

[1] https://www.psychologytoday.com/blog/how-we-do-it/201505/oxytocin-the-multitasking-love-hormone

[2] http://www.yourhormones.info/Hormones/Oxytocin.aspx

[3] http://rstb.royalsocietypublishing.org/content/361/1476/2187#sec-4

[4] http://www.medicalnewstoday.com/articles/275795.php

[5] Oxytocin: the great facilitator of life. Lee H-J, Macbeth AH, Pagani J, Young WS, Progress in Neurobiology, 2009, volume 88, issue 2, pages 127-151 (DOI: 10.1016/j.pneurobio.2009.04.001).

[6]http://www.mayoclinic.org/drugs-supplements/oxytocin-intravenous-route-intramuscular-route/description/drg-20065254

[7]Carmichael, M.S., Humbert, R., Dixen, J., Palmisano, G., Greenleaf, W. & Davidson, J.M. (1987) Plasma oxytocin increases in the human sexual response. Journal of Clinical Endocrinology & Metabolism 64:27-31.

[8]Carmichael, M.S., Warburton, V.L., Dixen, J. & Davidson, J.M. (1994) Relationships among cardiovascular, muscular, and oxytocin responses during human sexual activity.Archives of Sexual Behavior 23:59-79.

[9] Wildt, L., Kissler, S., Licht, P. & Becker, W. (1998) Sperm transport in the human female genital tract and its modulation by oxytocin as assessed by hysterosalpingoscintigraphy, hysterotonography, electrohysterography and Doppler sonography. Human Reproduction Update 4:655-666.

[10] http://rstb.royalsocietypublishing.org/content/361/1476/2187#sec-4

[11] The "Love Hormone" Oxytocin Helps Men Lose Weight, Says New Study, But What About Women? / Bustle / May 2015

[12] Alcohol, Love and Oytocin / The Vancouver Sun / May 29, 2015

[13] Oxytocin enhances brain reward system responses in men viewing the face of their female partner, René Hurlemann, et al., Proceedings of the National Academy of Sciences, doi: 10.1073/pnas.1314190110, published online 25 November 2013, Abstract.

[14] Dirk Scheele, Nadine Striepens, Onur Güntürkün, Sandra Deutschländer, Wolfgang Maier, Keith M. Kendrick, and René Hurlemann. "Oxytocin Modulates Social Distance between Males and Females". The Journal of Neuroscience, November 2012, doi: 10.1523/​JNEUROSCI.2755-12.2012

[15] Ditzen B1, Nater UM, Schaer M, La Marca R, Bodenmann G, Ehlert U, Heinrichs M. Sex-specific effects of intranasal oxytocin on autonomic nervous system and emotional responses to couple conflict. Soc Cogn Affect Neurosci. 2013 Dec;8(8):897-902. doi: 10.1093/scan/nss083. Epub 2012 Jul 27.

[16] 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

[17] http://en.wikipedia.org/wiki/Oxytocin

[18] http://www.concordia.ca/cunews/main/stories/2011/12/09/oxytocin-helps-people-feel-more-extroverted.html
[19] Patricia S. Churchlanda, Piotr Winkielmanb, Modulating social behavior with oxytocin: How does it work? What does it mean? Hormones and Behavior Volume 61, Issue 3, March 2012, Pages 392–399
[20] Abigail A. Marsh, Henry H. Yu, Daniel S. Pine, R. J. R. Blair Oxytocin improves specific recognition of positive facial expressions Psychopharmacology April 2010, Volume 209, Issue 3, pp 225-232
[21] McGregor IS, Callaghan PD, Hunt GE (May 2008). "From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use?". Br. J. Pharmacol. 154 (2): 358–368. doi:10.1038/bjp.2008.132.PMC 2442436. PMID 18475254. 

[22] http://intramural.nimh.nih.gov/lcmr/snge/History.html

[23] Weisman O, Zagoory-Sharon O, Feldman R (September 2012). "Intranasal oxytocin administration is reflected in human saliva". 

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[24]  Huffmeijer R, Alink LR, Tops M et al. (2012). "Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration". Neuro Endocrinol. Lett. 33 (1): 21–5.PMID 22467107.

[25] Lane A, Luminet O, Rimé B, Gross JJ, de Timary P, Mikolajczak M (2013). "Oxytocin increases willingness to socially share one's emotions". Int J Psychol 48 (4): 676–81.doi:10.1080/00207594.2012.677540. PMID 22554106.

[26] Theodoridou A, Rowe AC, Penton-Voak IS, Rogers PJ (June 2009). "Oxytocin and social perception: oxytocin increases perceived facial trustworthiness and attractiveness". Horm Behav 56(1): 128–32. doi:10.1016/j.yhbeh.2009.03.019. PMID 19344725.

[27] http://www.nature.com/nature/journal/v435/n7042/abs/nature03701.html

Nature 435, 673-676 (2 June 2005) | doi:10.1038/nature03701; Received 20 April 2005; Accepted 5 May 2005

Oxytocin increases trust in humans

Michael Kosfeld1,5, Markus Heinrichs2,5, Paul J. Zak3, Urs Fischbacher1 & Ernst Fehr1,4

[28] http://www.ncbi.nlm.nih.gov/pubmed/19747930

[29]  Theodoridou A, Penton-Voak IS, Rowe AC (2013). "A direct examination of the effect of intranasal administration of oxytocin on approach-avoidance motor responses to emotional stimuli". PLoS ONE 8 (2): e58113. doi:10.1371/journal.pone.0058113.PMC 3585234. PMID 23469148.

[30]  Huber D, Veinante P and Stoop R (April 2005). "Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala". Science 308 (5719): 245–8.doi:10.1126/SCIENCE.1105636. PMID 15821089.

[31] Viviani D, Charlet A, van den Burg E, Robinet C, Hurni N, Abatis M, Magara F, Stoop R. (July 2011). "Oxytocin selectively gates fear responses through distinct outputs from the central amygdala".Science 333 (6038): 104–7. doi:10.1126/SCIENCE.1201043.PMID 21719680.

[32] Shamay-Tsoory SG, Fischer M, Dvash J, Harari H, Perach-Bloom N, Levkovitz Y (November 2009). "Intranasal administration of oxytocin increases envy and schadenfreude (delight in the misfortunes of others)". Biological Psychiatry 66 (9): 864–70.doi:10.1016/j.biopsych.2009.06.009. PMID 19640508.

[33] Similar effects of intranasal oxytocin administration and acute alcohol consumption on socio-cognitions, emotions and behaviour: Implications for the mechanisms of action, Ian Mitchell, et al., Neuroscience and Biobehavioral Reviews, doi: http://dx.doi.org/10.1016/j.neubiorev.2015.04.018, published online 20 May 2015, abstract.

[34] http://www.medicaldaily.com/drunk-love-now-backed-science-alcohol-and-oxytocin-show-similar-brain-effects-334092

[35] http://www.nature.com/nature/journal/v488/n7410/full/nature11270.html

Atasoy, D; Betley, JN; Su, HH; Sternson, SM (9 August 2012). "Deconstruction of a neural circuit for hunger.". Nature 488 (7410): 172–7. doi:10.1038/nature11270. PMID 22801496.

[36] Shalvia, S.; De Dreu, C. K. W. "Oxytocin promotes group-serving dishonesty". Proceedings of the National Academy of Sciences of the United States of America 111 (15): 5503–07.doi:10.1073/pnas.1400724111. Lay summary – BBC News (2 April 2014).

[37] http://www.pnas.org/content/108/4/1262.abstract

Oxytocin promotes human ethnocentrism

Edited by Douglas S. Massey, Princeton University, Princeton, NJ, and approved December 21, 2010 (received for review October 12, 2010)

PNAS.ORG

[38] Oxytocin enhances brain function in children with autism

Edited by Leslie G. Ungerleider, National Institute of Mental Health, Bethesda, MD, and approved November 6, 2013 (received for review July 8, 2013)

[39] http://www.medicalnewstoday.com/articles/269630.php

[40]  Wang, H., Duclot, F., Liu, Y., Wang, Z. & Kabbaj, M. Nature Neurosci.http://dx.doi.org/10.1038/nn.3420 (2013).

[41] Gene switches make prairie voles fall in love / Nature.com / 2013

IMAGE CREDITS

Pygmalion and Galatea (1890) / New York’s Metropolitan Museum’s collection 

http://www.metmuseum.org/collection/the-collection-online/search/436483

Artist: Jean-Léon Gérôme (French, Vésoul 1824–1904 Paris)

"Hypothalamus small" by Images are generated by Life Science Databases(LSDB). - from Anatomography, website maintained by Life Science Databases(LSDB).You can get this image through URL below. 次のアドレスからこのファイルで使用している画像を取得できますURL.. Licensed under CC BY-SA 2.1 jp via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Hypothalamus_small.gif#/media/File:Hypothalamus_small.gif

Central and Peripheral Sites of Oxytocin Release (Gordon et al., 2011). http://www.ncbi.nlm.nih.gov/

Oxytocin Positive Feedback During Labour/ http://www.naturalbirthandbabycare.com/wp-content/uploads/2014/09/106_Pregnancy-Positive_Feedback.jpg

"Prairie vole" by United States National Park Service - Tallgrass Prairie National Preserve. Licensed under Public Domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Prairie_vole.gif#/media/File:Prairie_vole.gif

"Meadvole". Licensed under Public Domain via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Meadvole.jpg#/media/File:Meadvole.jpg