Effects of haloperidol in a response-reinstatement model of heroin relapse.

The present study employed an animal model of drug relapse in which previously extinguished heroin self-administration behavior was reinstated following a single reinforced trial. Male albino rats were trained to traverse a straight-alley for a reinforcer consisting of a single IV injection of 0.06 mg/kg diacetylmorphine (heroin). Once the alley-running had been established, the heroin reinforcer was removed and the operant behavior permitted to extinguish over trials. On treatment day, animals were injected 45 min prior to testing with 0.0, 0.075, 0.10, 0.15 or 0.3 mg/kg of the dopamine receptor antagonist, haloperidol. A single trial was then conducted during which some animals continued to experience extinction conditions while others were injected with the heroin reinforcer upon entry into the goal box. The effects of these manipulations were determined during an additional single test trial conducted 24 h later when the subjects were no longer drugged. While heroin produced a reliable reinstatement in operant responding, this effect was dose-dependently prevented by pretreatment with haloperidol. These data suggest that dopamine receptor antagonism alters the reinforcing consequences of heroin administration as measured by heroin's ability to reinstate operant behavior following a prolonged period of nonreinforced responding.