Cue-induced resumption of heroin and cocaine seeking in rats using a conflict model of abstinence and relapse

摘要

Rationale and objectives: Most animal research on drug relapse involves the reinstatement model where abstinence is a result of drug removal (extinction). However, abstinence in humans often results from the aversive consequences that accompany drug seeking (conflict situation). This study was aimed at using a conflict-based animal model of abstinence/relapse in rats self-administering heroin or cocaine. Methods: Rats were trained to self-administer heroin (0.05 mg kg-1 injection-1) or cocaine (0.5 mg kg-1 injection-1) with each injection paired with a light cue. After stable responding was demonstrated, the floor near the levers was electrified, creating a barrier, in order to model the negative consequences of continued drug seeking. Shock intensities were increased over sessions until no responses occurred for three consecutive sessions. During a relapse test, where shock was maintained,the capacity of noncontingent drug cue presentations to induce active lever pressing was assessed. Results: Ten of ten heroin animals and three of eight cocaine animals exposed to noncontingent cue presentations resumed responding. During the relapse test, for both drug groups, active lever pressing was significantly higher than during abstinence but only in the heroin group was it significantly higher than inactive lever pressing. Conclusions: The implementation of negative consequences for drug seeking can result in its cessation just as they might in human addicts. Similarly, exposure to drug cues can lead to resumption of drug seeking. This model may be useful for studying the mechanisms underlying abstinence and relapse and for developing strategies to prevent relapse.