Voluntary alcohol drinking enhances proopiomelanocortin (POMC) gene expression in nucleus accumbens shell and hypothalamus of Sardinian alcohol-preferring rats.

Background: Evidence obtained in humans and rodents indicates that beta-endorphin [encoded by the proopiomelanocortin (POMC) gene] is critical in regulation of alcohol drinking behavior. However, the alcohol effect on POMC gene expression has not been studied in rodent mesolimbic regions, such as the nucleus accumbens (NAc). Methods: In this study, we first utilized POMC-EGFP transgenic mice to visualize POMC neurons, and found that POMC-EGFP cells were modestly distributed throughout NAc shell and core, in addition to hypothalamic arcuate nucleus. POMC mRNA expression in NAc of mice and rats was confirmed using RT-PCR and solution hybridization assays. We then investigated whether there are genetically determined differences in basal mRNA levels of POMC and mu opioid receptor (MOP-r) between selectively bred Sardinian alcohol-preferring (sP) and -nonpreferring (sNP) rats, and if these mRNA levels are altered in sP after alcohol drinking (10%, unlimited access) for 17 days. Results: Alcohol-naive sP rats had higher basal POMC mRNA levels than sNP only in hypothalamus. Alcohol drinking increased POMC mRNA levels in both NAc shell (100%) and hypothalamus (50%) of sP. Although sP had lower basal levels of MOP-r mRNA and GTP?S binding in NAc shell than sNP rats, voluntary alcohol consumption had no effect on MOP-r mRNA levels in NAc shell. Conclusion: Our results define the distribution of POMC-expressing neurons in NAc of mice and rats. Higher POMC expression at basal levels in alcohol-preferring sP rats(genetically determined), along with increases after drinking (alcohol-induced) in NAc shell and hypothalamus, suggest that the POMC systems play a role in high alcohol preference and consumption.