Repeated ethanol administration induces short- and long-term changes in enkephalin and dynorphin tissue concentrations in rat brain.

Recently, we have shown that rats repeatedly treated with ethanol and/or cocaine have decreased kappa-opioid receptor mRNA levels in the mesolimbic system. The aim of the present study was to investigate the short- and long-term effects of repeated ethanol administration on opioid peptide concentrations in brain tissue of male Sprague-Dawley rats. Dynorphin B (1-13) (Dyn B) and Met-enkephalinArg(6)Phe(7) (MEAP), endogenous ligands to kappa- and delta-opioid receptors, respectively, were measured using radioimmunoassays. The rats were given either ethanol [intraperitoneal (ip), twice daily, 2 g/kg bw/dose] or saline for 13 consecutive days. Thirty minutes after the last ethanol dose on Day 13, the Dyn B tissue concentration was significantly decreased in the cingulate cortex. The MEAP tissue concentration was decreased in the hippocampus 5 days after the last ethanol injection as compared to saline-treated controls. Furthermore, the Dyn B and the MEAP concentrations were increased in the periaqueductal grey area (PAG) at this time point. Of particular interest were the significant increases in Dyn B tissue concentrations found in the nucleus accumbens (NAcc) at 30 min and at 21 days after the last ethanol dose. The results suggest that repeated ethanol administration induces both short- and long-term changes in the tissue concentrations of opioids in certain brain regions associated with motivation and reward.