Naltrexone effects on ethanol reward and discrimination in C57BL/6 mice

The effects of the opioid antagonist, naltrexone, on operant responding for oral ethanol reward delivered on a fixed-ratio schedule, acid on the discr iminative stimulus properties of intraperitoneally injected ethanol, was ex amined in two separate experiments. The ages, food/water motivational condi tions, and naltrexone doses for the two experiments were similar to allow a direct comparison of naltrexone effects on the two measures. Male food-dep rived C57BL/6 mice responded for ethanol during either preprandial (low thi rst, high hunger motivation) or postprandial (high thirst, low hunger motiv ation tests). The reinforcing value of ethanol relative to water was greate r during the preprandial tests; however, the amounts of ethanol consumed wa s greater during the postprandial tests, with same mice becoming unconsciou s during the 15-min test session. Naltrexone produced dose-responsive reduc tions in responding for ethanol under either testing condition. During post prandial tests, naltrexone reduced responding for ethanol reward at a dose (1.25 mg/kg) that had little effect on responding for water reward, suggest ing some selectivity for ethanol reward. In addition, doses of naltrexone t hat reduced responding for ethanol rewards did not alter the discrimination of ethanol (g/kg) in an operant discrimination task, but did reduce the to tal number of responses made during these tests. Thus, under similar motiva tional and dosing conditions, the opiate antagonist attenuated the reinforc ing, but not the discriminative properties of ethanol, suggesting that the latter is mediated by either different or additional neural mechanisms in C 57BL/6 mice.