Increased ethanol drinking in "humanized" mice expressing the mu opioid receptor A118G polymorphism are mediated through sex-specific mechanisms.

Increased ethanol drinking in "humanized" mice expressing the mu opioid receptor A118G polymorphism are mediated through sex-specific mechanisms. Brain Res Bull. 2017 Aug 02;: Authors: Henderson-Redmond AN, Lowe TE, Tian XB, Morgan DJ Abstract The A118G single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (Oprm1) has been implicated in mediating the rewarding effects of alcohol. Clinical and preclinical studies suggest that the G allele may confer a genetic vulnerability to alcohol dependence, though it remains unknown whether these effects are sex-specific. We used male and female mice homozygous for the "humanized" 118AA or 118GG alleles to determine whether the A118G SNP potentiates ethanol consumption in a sex-specific manner in both the two-bottle choice and drinking-in-the-dark (DID) paradigms. Mice were also assessed for differences in naltrexone sensitivity, ethanol reward assessed via conditioned place preference (CPP), and sensitivity to the sedative/ataxic effects of ethanol using the rota-rod and loss of righting reflex (LORR) assays. We found that male and female 118GG mice drank significantly more ethanol than 118AA littermates using a continuous access, two-bottle choice paradigm. In the limited-access DID drinking model, (i) female (but not male) 118GG mice consumed more ethanol than 118AA mice and (ii) naltrexone pretreatment was equally efficacious at attenuating ethanol intake in both 118AA and 118GG...
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research