The influence of opioid antagonists on the discriminative stimulus effects of ethanol

The aim of the present study was to investigate the role of different endogenous opioid systems in the expression of ethanol's discriminative stimulus effects in a two-lever operant drug discrimination paradigm. Wistar rats trained to make differential responses following the administration of ethanol (1 g/kg, i.p.) or saline. The correct response (fixed-ratio schedule; FR10) resulted in the presentation of food. Once rats had acquired the discrimination an ethanol dose-response test was conducted. The effects of opioid antagonists on the discrimination were assessed by administering the mu-opioid receptor antagonists naloxone (0.5-20 mg/kg s.c.) and cyprodime (5-100 mg/kg s.c.) and the delta-opioid receptor antagonist naltrindole (0.1-25 mg/kg s.c.) 15-30 min before the discrimination test. Furthermore, the selective kappa-opioid antagonist nor-binaltorphimine (5 mg/kg s.c.) given 24 h before the test session was examined. Results of generalization testing demonstrate that ethanol discrimination was dose dependent. Pretreatment with naloxone produced only at the highest dose a partial, but significant, antagonism, whereas cyprodime failed to alter the ethanol cue. This suggested the involvement of other opioid receptor subtypes. However, neither naltrindole nor nor-binaltorphimine had any effect on the ethanol-saline discrimination. These results demonstrate that the expression of the ethanol cue is only partly dependent on the function of endogenous opioid systems.