DRD1 5'UTR variation, sex and early infant stress influence ethanol consumption in rhesus macaques

The mesolimbic dopamine system plays an important role in mediating a variety of behaviors and is involved in mediating the reinforcing effects of ethanol. Genes encoding dopamine receptor subtypes are thus good candidate loci for understanding the genetic etiologies of susceptibility to alcohol dependence and its antecedent behavioral phenotypes. We tested whether variation in DRD1 influences alcohol consumption in rhesus macaques and whether its influence is mediated by sex and early rearing experience. We genotyped a single nucleotide polymorphism (-111 G/T) in the 5'UTR of DRD1 in 96 subjects raised with their mothers until 6 months of age (n = 43) or in peer-only groups (n = 53). As young adults they underwent a 7-week voluntary ethanol consumption experiment. anova revealed a significant main effect of sex (F-1,F-95 = 6.3, P = 0.014) and an interaction between genotype, sex and rearing on ethanol consumption (F-7,F-95 = 4.63, P = 0.0002). Maternally deprived males heterozygous for the T allele consumed significantly more ethanol (P > t < 0.0001) than the other subgroups. Maternal deprivation can produce individuals that are anxious and impulsive, both of which are known risk factors for alcohol dependence. Our work demonstrates a potential role for the dopamine D1 receptor gene in modulating alcohol consumption, especially in the context of early environmental stress.