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.
Broadbent
J
J
Department of Behavioral Neuroscience, Oregon Health Sciences University, Portland 97201-3098, USA.
Linder
H V
HV
Cunningham
C L
CL
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005824:Genetics, Behavioral; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009270:Naloxone / Q000494:pharmacology*; D013649:Taste / Q000187:drug effects* / Q000235:genetics
D009270:Naloxone; D000431:Ethanol