EFFECTS OF BUPRENORPHINE AND NALTREXONE ON REINSTATEMENT OF COCAINE-REINFORCED RESPONDING IN RATS

Reinstatement of responding previously maintained by cocaine was measu red after noncontingent ''priming'' injections of cocaine, the opioid partial agonist buprenorphine, the opioid antagonist naltrexone and th e opioid agonist etonitazene. The effects of pretreatment with bupreno rphine, naltrexone or etonitazene on the reinstatement of responding p roduced by a priming injection of cocaine were also evaluated. The rat s were trained to respond on a lever under a fixed-ratio 1 schedule to receive i.v. infusions of cocaine (1.0 mg kg-1 infusion-1) for the in itial 2 hr during daily 7-hr sessions. Saline replaced cocaine at the beginning of hour 3, which resulted in an extinction of responding dur ing the third hour and low levels of responding during the subsequent 4 hr of the session. Priming i.v. injections of cocaine (0.4-3.2 mg/kg ), but not buprenorphine (0.025-0.4 mg/kg), naltrexone (1.6 and 3.2 mg /kg) or etonitazene (2.5 and 5.0 mug/kg), administered at the beginnin g of hour 4 of the session (i.e., during the extinction period), produ ced a dose-related reinstatement of responding. Pretreatment with eith er buprenorphine (0.025-0.4 mg/kg) or etonitazene (2.5 and 5.0 mug/kg) , but not naltrexone (1.6 and 3.2 mg/kg), produced a dose-related supp ression of the reinstatement of responding produced by 3.2 mg/kg of co caine. These results indicate that 1) buprenorphine and naltrexone hav e little potential for producing reinstatement of responding in cocain e-maintained rats and 2) buprenorphine's effectiveness in preventing a reinstatement of responding produced by a cocaine priming injection m ay be related to its opioid agonist actions.