The effect of chronic naltrexone pretreatment on associative vs. non-associative morphine tolerance

The purpose of this study was to examine the effect of chronic naltrexone on associative and non-associative morphine tolerance. Rats were given nine injections of either naltrexone (5 mg/kg) or saline during a 5 day period. Following this pretreatment, all rats received 6 morphine injections (5 mg/kg) during the next 14 days. For half the rats in each pretreatment condition, morphine was injected in a distinctive room (paired) while the other half received morphine in the home cage (unpaired). All rats were given the seventh morphine injection (5 mg/kg) in the distinctive room and tested for analgesia. Context-specific tolerance was found in both pretreatment conditions. Compared to pretreatment with saline, naltrexone pretreatment produced more analgesia in the unpaired condition but had no effect in the paired condition. These results suggest that antagonist pretreatment attenuated tolerance that was not mediated by explicit environmental cues but had no effect on context-specific analgesic tolerance.