Endocannabinoid signaling mediates oxytocin-driven social reward

Evidence that an oxytocin-dependent endocannabinoid
signal contributes to the regulation of social reward.
The results provide insights into the functions of oxytocin, a
neuropeptide crucial for social behavior, and its interactions
with other modulatory systems that regulate the rewarding
properties of social behavior. They further suggest that oxytocin-
driven anandamide signaling may be defective in autism
spectrum disorders, and that correcting such deficits might offer a
strategy to treat these conditions.

Authors: D Wei, D Dinh, D Lee, A Anguren, G Moreno-Sanz, C Gall, D Piomelli

Cannabis and Cannabinoid Research (2016)1:81-89

Clinical Trials, Studies and Publications (click to access):

Enhancement of Anandamide-Mediated Endocannabinoid Signalling Corrects Autism-Related Social Impairment

Deficits in cannabinoid signalling may contribute to social impairment in autism spectrum disorders.

It has been suggested that oxytocin can improve social, emotional and behavioral problems in autistic children although comprehensive clinical studies are still required. This article describes a mouse model where anandamide-mediated signalling of CB1 receptors controls social reward that is driven by oxytocin. These results suggest that anandamide, a THC analog, may offer an avenue to improve behavior in austism spectrum disorders.

Abstract:

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 anandamidemediated
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.

Authors: D Wei, D Lee, CD Cox, CA Karsten, O Penagarikano, DH Geschwind, CM Gall, D Piomelli

PNAS (2015) 112: 14084-14089

Clinical Trials, Studies and Publications (click to access):

Endocannabinoid signaling mediates oxytocin-driven social reward.