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

Learn how you can help with a new
Autism, ADHD, Anxiety & Depression study.

CAR stands united with the Black Lives Matter movement
against racism and social injustice. Read more...

TitleMouse model of OPRM1 (A118G) polymorphism increases sociability and dominance and confers resilience to social defeat.
Publication TypeJournal Article
Year of Publication2015
AuthorsBriand, LA, Hilario, M, Dow, HC, Brodkin, ES, Blendy, JA, Berton, O
JournalJ Neurosci
Volume35
Issue8
Pagination3582-90
Date Published2015 Feb 25
ISSN1529-2401
KeywordsAggression, Anhedonia, Animals, Dominance-Subordination, Female, Heterozygote, Male, Mice, Mice, Inbred C57BL, Mutation, Missense, Naloxone, Narcotic Antagonists, Nucleus Accumbens, Periaqueductal Gray, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-fos, Receptors, Opioid, mu
Abstract

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.

DOI10.1523/JNEUROSCI.4685-14.2015
Alternate JournalJ Neurosci
PubMed ID25716856
PubMed Central IDPMC4339361
Grant ListR21 DA027066 / DA / NIDA NIH HHS / United States
R01 MH080718 / MH / NIMH NIH HHS / United States
P50MH096891-6773 / MH / NIMH NIH HHS / United States
R21-DA-027066 / DA / NIDA NIH HHS / United States
K99 DA033372 / DA / NIDA NIH HHS / United States
K99DA033372 / DA / NIDA NIH HHS / United States
R01MH087581 / MH / NIMH NIH HHS / United States
R01 DA033646 / DA / NIDA NIH HHS / United States
R01DA033646 / DA / NIDA NIH HHS / United States
R01 MH087581 / MH / NIMH NIH HHS / United States
U54 HD086984 / HD / NICHD NIH HHS / United States
R01MH080718 / MH / NIMH NIH HHS / United States
Comments
Leave a Comment