Discriminative stimulus effects of naltrexone in rats with limited access to sucrose

Abstract

Naltrexone, an opioid antagonist, is not discriminable at typical doses in operant paradigms. We attempted to establish naltrexone as a discriminative stimulus in rats given 12-hour dark cycle access to sucrose solutions. Interestingly, acute water substitution did not alter the discriminative stimulus effects, suggesting that sucrose consumption produced a long-term change in endorphin function. Chronic (two-week) water substitution eliminated the discriminative stimulus effects of naltrexone. Following chronic water substitution, subjects were again given daily 12-hour dark cycle access to sucrose and 12-hour light cycle access to water for two weeks. Subjects then resumed training, which resulted in rapid reacquisition of the 3.2 mg/kg naltrexone discrimination. Restoring daily sucrose access resulted in all subjects rapidly reacquiring the NTX and saline discrimination. Naltrexone 0.1 mg/kg was discriminable by several subjects. We are currently attempting to train the subjects to reacquire the discrimination of 0.1 mg/kg NTX. Our results suggest that chronic sucrose consumption results in a long term change in endogenous opioid activity.