Effects of the selective mu(1)-opioid receptor antagonist, naloxonazine, on cocaine-induced conditioned place preference and locomotor behavior in rats.

Administration of the non-selective opioid receptor antagonists, naloxone and naltrexone, attenuate the rewarding effects of cocaine. The relative contributions of specific opioid receptor subtypes that underlie this effect have not been well characterized. Administration of 20.0 mg/kg cocaine resulted in a conditioned place preference. Pretreatment with 20.0 mg/kg but neither 10.0 nor 1.0 mg/kg of the selective mu(1)-opioid receptor antagonist, naloxonazine, blocked cocaine-induced conditioned place preference. On the days in which rats received cocaine only, locomotor behavior was elevated. Pretreatment with the selective mu(1)-opioid receptor antagonist, naloxonazine, regardless of dose, had no effect on cocaine-induced hyperlocomotion. These findings indicate that the rewarding effects of cocaine can be blocked solely by mu(1)-opioid receptor antagonism and are consistent with the view that the locomotor and rewarding effects of drugs can be dissociated.