Naloxone depresses cocaine self-administration and delays its initiation on the following day.

Abstract

While dopamine mechanisms play a crucial role in cocaine-taking behavior, the contribution of endogenous opioid systems is less clear. We assessed the effects of opioid receptor blockade by naloxone (1 mg/kg, s.c.) on the daily performance and subsequent initiation of cocaine self-administration in trained rats. Naloxone decreased self-administration rate by approximately half, with the effect varying from complete blockade to no change. On the day following naloxone treatment, the latencies from the drug availability cue to the first self-administration were consistently longer than before naloxone treatment. Measurement of brain temperature and behavioral observations suggested a lower than normal level of motivational arousal as a factor for slow initiation of cocaine-taking behavior. After the first drug infusion, however, performance was uniformly normal. These data suggest endogenous opioid systems play a role in cocaine-taking behavior and indicate a residual inhibitory consequence of naloxone treatment on the initiation of this behavior.