Oprm1 A112G, a single nucleotide polymorphism, alters expression of stress-responsive genes in multiple brain regions in male and female mice.

BACKGROUND: OPRM1 A118G, a functional human mu-opioid receptor (MOR) polymorphism, is associated with drug dependence and altered stress responsivity in humans as well as altered MOR signaling. MOR signaling can regulate many cellular processes, including gene expression, and many of the long-term, stable effects of drugs and stress may stem from changes in gene expression in diverse brain regions. A mouse model bearing an equivalent polymorphism (Oprm1 A112G) was previously generated and studied. Mice homozygous for the G112 allele show differences in opioid- and stress-related phenotypes.

APPROACH: The current study examines the expression of 24 genes related to drug and stress responsivity in the caudoputamen, nucleus accumbens, hypothalamus, hippocampus, and amygdala of drug-naïve, stress-minimized, male and female mice homozygous for either the G112 variant allele or the wild-type A112 allele.

RESULTS: We detected nominal genotype-dependent changes in gene expression of multiple genes. We also detected nominal sex-dependent as well as sex-by-genotype interaction effects on gene expression. Of these, four genotype-dependent differences survived correction for multiple testing: Avp and Gal in the hypothalamus and Oprl1 and Cnr1 in the hippocampus.

CONCLUSIONS: Changes in the regulation of these genes by mu-opioid receptors encoded by the G112 allele may be involved in some of the behavioral and molecular consequences of this polymorphism observed in mice.