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UCI study uncovers role of oxytocin in triggering marijuana-like neurotransmitters.
The hormone oxytocin, which has been associated with interpersonal bonding, may enhance the pleasure of social interactions by stimulating production of marijuana-like neurotransmitters in the brain, according to a University of California, Irvine study.
The research provides the first link between oxytocin – dubbed the “love hormone” – and anandamide, which has been called the “bliss molecule” for its role in activating cannabinoid receptors in brain cells to heighten motivation and happiness. Results appear the week of Oct. 26 in the early online edition of Proceedings of the National Academy of Sciences.
To investigate the role of anandamide in social contact, UCI’s Daniele Piomelli – the Louise Turner Arnold Chair in the Neurosciences and founding director of the drug discovery & development department at the Italian Institute of Technology in Genoa, Italy – and his colleagues measured levels of this marijuana-like neurotransmitter in mice that had been either isolated or allowed to interact. Anandamide is among a class of naturally occurring chemicals in the body known as endocannabinoids that attach to the same brain cell receptors as does marijuana’s active ingredient, THC, with similar outcomes.
The researchers discovered that social contact increased production of anandamide in a brain structure called the nucleus accumbens, which triggered cannabinoid receptors there to reinforce the pleasure of socialization. When cannabinoid receptors were blocked, this reinforcement disappeared.
Piomelli’s team then looked for a possible connection between anandamide and oxytocin, which is well known for its role in promoting social contact. A small number of neurons in the brain make oxytocin and use it as a neurotransmitter. When the scientists stimulated those neurons, they saw an increase in anandamide creation in the nucleus accumbens. More importantly, they found that blocking anandamide’s effects also blocked the pro-social effects of oxytocin, which implies that oxytocin reinforces social ties by inducing anandamide formation.
Adding medical interest to this discovery, the researchers showed that interrupting anandamide degradation enhanced the pleasure of social contact. Animals treated with a drug that stops anandamide degradation behaved as though they enjoyed spending time with their cage mates more than animals treated with a placebo, Piomelli noted.
Oxytocin has also been called the hug hormone, cuddle chemical and moral molecule due to its effects on behavior, including its role in love and female reproductive functions. A 2011 study by Dutch scientists revealed that oxytocin makes people feel more extroverted, and clinical researchers are investigating it as a possible treatment for the symptoms of autism. But it’s very hard to deliver oxytocin, a small protein, to the human brain.
“Our findings open the exciting possibility that drugs that block the degradation of anandamide, which are currently being tested for various anxiety disorders, could give a boost to the brain’s own oxytocin and help people with autism socialize more,” Piomelli said.
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Funding: Christine Gall, Don Wei, DaYeon Lee, Conor Cox and Carley Karsten of UCI; Dr. Daniel Geschwind of UCLA; and Olga Peñagarikano of the University of the Basque Country in Spain contributed to the research, which was supported by the National Institutes of Health (grant DA012413), the UCI Medical Scientist Training Program and the UCI Center for Autism Research & Translation.
Source: Tom Vasich – UC Irvine Image Credit: The image is credited to McGill University and is licensed CC BY-SA 3.0 Original Research: Abstract for “Endocannabinoid signaling mediates oxytocin-driven social reward” by Don Wei, DaYeon Lee, Conor D. Cox, Carley A. Karsten, Olga Peñagarikano, Daniel H. Geschwind, Christine M. Gall, and Daniele Piomelli in PNAS. Published online October 26 2015 doi:10.1073/pnas.1509795112
Endocannabinoid signaling mediates oxytocin-driven social reward
Marijuana exerts profound effects on human social behavior, but the neural substrates underlying such effects are unknown. Here we report that social contact increases, whereas isolation decreases, the mobilization of the endogenous marijuana-like neurotransmitter, anandamide, in the mouse nucleus accumbens (NAc), a brain structure that regulates motivated behavior. Pharmacological and genetic experiments show that anandamide mobilization and consequent activation of CB1 cannabinoid receptors are necessary and sufficient to express the rewarding properties of social interactions, assessed using a socially conditioned place preference test. We further show that oxytocin, a neuropeptide that reinforces parental and social bonding, drives anandamide mobilization in the NAc. Pharmacological blockade of oxytocin receptors stops this response, whereas chemogenetic, site-selective activation of oxytocin neurons in the paraventricular nucleus of the hypothalamus stimulates it. Genetic or pharmacological interruption of anandamide degradation offsets the effects of oxytocin receptor blockade on both social place preference and cFos expression in the NAc. The results indicate that anandamide-mediated signaling at CB1 receptors, driven by oxytocin, controls social reward. Deficits in this signaling mechanism may contribute to social impairment in autism spectrum disorders and might offer an avenue to treat these conditions.
“Endocannabinoid signaling mediates oxytocin-driven social reward” by Don Wei, DaYeon Lee, Conor D. Cox, Carley A. Karsten, Olga Peñagarikano, Daniel H. Geschwind, Christine M. Gall, and Daniele Piomelli in PNAS. Published online October 26 2015 doi:10.1073/pnas.1509795112
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