The delta-opioid receptor antagonist naltrindole prevents sensitization to the conditioned rewarding effects of cocaine.

A conditioned place preference paradigm was used to determine whether: (i) prior exposure to cocaine results in an enhancement of its rewarding effects, and (ii) the delta-opioid receptor antagonist naltrindole can prevent the development of this response. Rats received daily injections of saline or cocaine (10.0 mg/kg i.p.) for 5 days in the colony room. Additional animals received naltrindole (0.03-0.3 mg/kg s.c.), lithium chloride (20 mg/kg s.c.) or vehicle prior to i.p. injections. Conditioning sessions (2 drug; 2 vehicle) commenced 3 days later. Cocaine (1.0-10.0 mg/kg) was ineffective as a conditioning stimulus in saline pre-exposed rats. In cocaine pre-exposed animals, however, doses of 5.0 and 10.0 mg/kg cocaine resulted in significant drug-induced place preferences. Significant cocaine-induced place preferences were also observed in animals which had received lithium chloride with the cocaine treatment regimen. In animals which had received naltrindole together with the chronic cocaine treatment regimen, cocaine failed to produce a conditioned response. These data demonstrate that the repeated administration of cocaine results in an enhancement of its rewarding effects (e.g. sensitization) and that this phenomenon is prevented by a delta-opioid receptor antagonist. Furthermore, the finding that naltrindole does not modify the acute rewarding effects of cocaine suggests a specific role of delta-opioid receptors in the sensitization process.