Effects of buprenorphine and naltrexone on reinstatement of cocaine-reinforced responding in rats.

Reinstatement of responding previously maintained by cocaine was measured after noncontingent "priming" injections of cocaine, the opioid partial agonist buprenorphine, the opioid antagonist naltrexone and the opioid agonist etonitazene. The effects of pretreatment with buprenorphine, naltrexone or etonitazene on the reinstatement of responding produced by a priming injection of cocaine were also evaluated. The rats 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 initial 2 hr during daily 7-hr sessions. Saline replaced cocaine at the beginning of hour 3, which resulted in an extinction of responding during 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 micrograms/kg), administered at the beginning of hour 4 of the session (i.e., during the extinction period), produced a dose-related reinstatement of responding. Pretreatment with either buprenorphine (0.025-0.4 mg/kg) or etonitazene (2.5 and 5.0 micrograms/kg), but not naltrexone (1.6 and 3.2 mg/kg), produced a dose-related suppression of the reinstatement of responding produced by 3.2 mg/kg of cocaine. These results indicate that 1) buprenorphine and naltrexone have little potential for producing reinstatement of responding in cocaine-maintained rats and 2) buprenorphine's effectiveness in preventing a reinstatement of responding produced by a cocaine priming injection may be related to its opioid agonist actions.