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 heated with ethanol and/or coc aine have decreased kappa -opioid receptor mRNA levels in the mesolimbic sy stem. The aim of the present study was to investigate the short- and long-t erm effects of repeated ethanol administration on opioid peptide concentrat ions 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 d elta -opioid receptors, respectively, were measured using radioimmunoassays . The rats were given either ethanol [intraperitoneal tip), twice daily, 2 g/kg bw/dose] or saline for 13 consecutive days. Thirty min after the last ethanol dose on Day 13, the Dyn B tissue concentration was significantly de creased in the cingulate cortex. The MEAP tissue concentration was decrease d in the hippocampus 5 days after the last ethanol injection as compared to saline-treated controls. Furthermore, the Dyn B and the MEAP concentration s were increased in the periaqueductal grey area (PAG) at this time point. Of particular interest were the significant increases in Dyn B tissue conce ntrations found in the nucleus accumbens (NAcc) at 30 min and at 21 days af ter the last ethanol dose. The results suggest that repeated ethanol admini stration induces both short- and long-term changes in the tissue concentrat ions of opioids in certain brain regions associated with motivation and rew ard. (C) 2001 Elsevier Science Inc. All rights reserved.