Mouse model of OPRM1 (A118G) polymorphism increases sociability and dominance and confers resilience to social defeat.

Lisa A Briand, Monica Hilario, Holly C Dow, Edward S Brodkin, Julie A Blendy, Olivier Berton

The Journal of neuroscience : the official journal of the Society for Neuroscience 2015 Feb 25

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A single nucleotide polymorphism (SNP) in the human μ-opioid receptor gene (OPRM1 A118G) has been widely studied for its association in drug addiction, pain sensitivity, and, more recently, social behavior. The endogenous opioid system has been shown to regulate social distress and reward in a variety of animal models. However, mechanisms underlying the associations between the OPRM1 A118G SNP and these behaviors have not been clarified. We used a mouse model possessing the human equivalent nucleotide/amino acid substitution to study social affiliation and social defeat behaviors. In mice with the Oprm1 A112G SNP, we demonstrate that the G allele is associated with an increase in home-cage dominance and increased motivation for nonaggressive social interactions, similar to what is reported in human populations. When challenged by a resident aggressor, G-allele carriers expressed less submissive behavior and exhibited resilience to social defeat, demonstrated by a lack of subsequent social avoidance and reductions in anhedonia as measured by intracranial self-stimulation. Protection from social defeat in G-allele carriers was associated with a greater induction of c-fos in a resilience circuit comprising the nucleus accumbens and periaqueductal gray. These findings led us to test the role of endogenous opioids in the A112G mice. We demonstrate that the increase in social affiliation in G carriers is blocked by pretreatment with naloxone. Together, these data suggest a mechanism involving altered hedonic state and neural activation as well as altered endogenous opioid tone in the differential response to aversive and rewarding social stimuli in G-allele carriers. Copyright © 2015 the authors 0270-6474/15/353582-09$15.00/0.

Citation

Lisa A Briand, Monica Hilario, Holly C Dow, Edward S Brodkin, Julie A Blendy, Olivier Berton. Mouse model of OPRM1 (A118G) polymorphism increases sociability and dominance and confers resilience to social defeat. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2015 Feb 25;35(8):3582-90