The Effect of Heroin Dependence on the Resumption of Heroin Self-administration after a Period of Abstinence and Extinction

It has been proposed that relapse vulnerability in previously dependent individuals results from augmentation of drug-induced reinforcement due to repeated associations between the interoceptive properties of the drug and reduction of acute withdrawal distress. To test this hypothesis, male Sprague-Dawley rats self-administered 0.05 mg/kg/inf heroin on continuous and progressive ratio (PR) schedules. During this period, they also received injections of vehicle or escalating doses of heroin. Following tests of naloxone-precipitated withdrawal (0.01 or 0.1 mg/kg, SC), as well as abstinence (4 days), and extinction training (9 sessions), they were pre-treated with vehicle or yohimbine (0.5 mg/kg, IV) and tested for resumption of heroin self-administration (0.05 mg/kg/inf) on continuous and PR schedules (Experiments 1 & 2), or tested for reinstatement in extinction conditions. Differences between vehicle- and heroin-injected rats were noted on self-administration on the continuous reinforcement schedule, but not on the PR schedule, in spite of greater signs of withdrawal precipitated by naloxone in the heroin-injected rats. More importantly, there were no group differences in resumption of heroin self-administration, and this was not altered by yohimbine. These results suggest that relapse vulnerability cannot be uniquely ascribed to the altered reinforcing action of drugs; contextual and other conditioning factors must play a role in modulating resumption of drug intake after periods abstinence.