Enhanced sensitivity of the nucleus accumbens proenkephalin system to alcohol in rats selectively bred for alcohol preference

Evidence suggests that alcohol-induced activation of the endogenous opioid system is part of a neurobiological mechanism that may be functionally involved in alcohol reinforcement and high alcohol drinking behavior. We postulate that a genetic predisposition toward alcohol drinking is accompanied by increased responsiveness of the opioid system to alcohol. To test this hypothesis, the present study compared the effect of an acute alcohol challenge on enkephalin gene expression in discrete brain regions which are high in preproenkephalin (PPENK) mRNA content and/or are important in mediating alcohol reward in rats selectively bred for alcohol preference (P) or nonpreference (NP). PPENK mRNA content was measured by in situ hybridization performed with a 36 base oligonucleotide probe for PPENK mRNA and was quantified using a computerized image-analysis system. Blood alcohol concentration (BAC) and rate of alcohol elimination following alcohol infusion were similar in P and NP rats. P and NP rats did not differ in basal content of PPENK mRNA in any of the brain areas examined prior to onset of infusion. An intragastric (I.G.) infusion of alcohol (2.5 g/kg b.wt) produced a significant increase in PPENK mRNA in the nucleus accumbens (both shell and core) of P but not NP rats at 1 h after the onset of infusion which coincided with the time at which peak BAC was attained. In contrast, at 8 h after the onset of the alcohol infusion, when BAC was falling toward baseline, PPENK mRNA was decreased in the nucleus accumbens of both P and NP rats and in the anterior striatum and amygdala of NP rats. The results suggest that enhanced responsiveness of the enkephalinergic system to alcohol is associated with, and may be functionally involved in, mediating high alcohol drinking behavior.