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 reward ing effects, and (ii) the delta-opioid receptor antagonist naltrindole can prevent the development of this response. Rats received daily inj ections of saline or cocaine (10.0 mg/kg i.p.) for 5 days in the colon y 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. Coc aine (1.0-10.0 mg/kg) was ineffective as a conditioning stimulus in sa line pre-exposed rats. In cocaine pre-exposed animals, however, doses of 5.0 and 10.0 mg/kg cocaine resulted in significant drug-induced pla ce preferences. Significant cocaine-induced place preferences were als o observed in animals which had received lithium chloride with the coc aine treatment regimen. In animals which had received naltrindole toge ther with the chronic cocaine treatment regimen, cocaine failed to pro duce a conditioned response. These data demonstrate that the repeated administration of cocaine results in an enhancement of its rewarding e ffects (e.g. sensitization) and that this phenomenon is prevented by a delta-opioid receptor antagonist. Furthermore, the finding that naltr indole does not modify the acute rewarding effects of cocaine suggests a specific role of delta-opioid receptors in the sensitization proces s.