THE EFFECT OF ETHANOL DRINKING ON OPIOID ANALGESIA AND RECEPTORS IN MICE

Recent studies suggest substantial interactions between opioids and et hanol (EtOH). Both in vivo and in vitro experiments indicate that EtOH can regulate opioid systems and that opioids can modify EtOH consumpt ion. In the present studies, we examined if EtOH consumption altered o pioid receptors and the potency of opioid analgesics. Mice were given unlimited access to 6-7% EtOH alone for 7 days or were allowed to drin k increasing concentrations (3-6%) of EtOH over 13-14 days. Controls h ad access to water. The EtOH groups drank significantly less volume th an controls, although there were no significant differences in body we ight or baseline nociception. The analgesic (tail nick) potency of SC morphine was decreased by similar to 1.6-2.0-fold in EtOH-treated mice . A single acute dose of EtOH (1 g/kg) that produced blood alcohol lev els in excess of that for 7 day exposure to EtOH, did not change morph ine's analgesic ED50, suggesting that chronic exposure to EtOH was nec essary for the reduction in potency. The change in morphine potency wa s not due to pharmacokinetic differences because EtOH consumption did not modify the concentration of morphine in brain and spinal cord. The analgesic potency of a delta-opioid receptor agonist (ICV DSLET) was also decreased by similar to 2-fold. Saturation binding studies indica ted no changes in the density or affinity of brain and spinal cord del ta-opioid ([H-3]DPDPE, [H-3]DSLET, [H-3]DeltorphinII) and mu-opioid ([ H-3]DAMGO) receptors. Similarly, there was no significant effect of Et OH on delta-opioid receptor mRNA in either brain or spinal cord prepar ations. Taken together, these data suggest that EtOH consumption decre ases the analgesic potency of opioids in mice through a mechanism that is unrelated to pharmacokinetics or opioid receptor changes in brain and cord. (C) 1997 Elsevier Science Inc.