Genetic differences in naloxone enhancement of ethanol-induced conditioned taste aversion

The influence of the opioid system on acquisition of an ethanol-induced conditioned taste aversion was examined in alcohol-preferring and avoiding inbred strains of mice (C57BL/6J and DBA/2J). Fluid-deprived mice from each strain received either ethanol alone, naloxone alone, or both ethanol and naloxone immediately after access to a novel tasting fluid. Naloxone alone (1 or 3 mg/kg) did not induce a conditioned taste aversion in either strain of mice. Administration of ethanol (1.5 g/kg) to DBA/2J mice produced a moderate taste aversion that was not affected by co-administration of naloxone. Although ethanol administered alone (3 g/kg) did not cause a taste aversion in C57BL/6J mice, the combination of ethanol and the higher dose of naloxone produced a significant taste aversion that increased across trials. A second experiment addressed the possibility that naloxone failed to enhance the ethanol-induced condition taste aversion in DBA/2J mice due to a floor effect on consumption. A lower ethanol dose (1 g/kg) was given alone or in combination with naloxone (1 or 3 mg/kg). Again, ethanol produced a moderate conditioned taste aversion that was not potentiated by naloxone. Subsequent conditioning with a high ethanol dose produced further suppression of intake, confirming that naloxone's failure to enhance aversion on earlier trials was not due to a floor effect. These data demonstrate a strain specific interaction between the aversive effect of ethanol and naloxone. More specifically, the results indicate that blockade of opioid receptors enhances the aversive effect of ethanol in C57BL/6J but not DBA/2J mice, suggesting that genetically determined differences in the endogenous opioid system of alcohol-preferring mice may mitigate ethanol's aversive effect.