Low dose of heroin inhibits drug-seeking elicited by cues after prolonged withdrawal from heroin self-administration in rats.

Environmental stimuli and conditioned cues associated with heroin can induce drug-seeking behavior, but how heroin lapse interacts with cues is unclear. Rats were trained to nose-poke for i.v. heroin for 14 days and then tested for heroin seeking after withdrawal from heroin self-administration. Heroin seeking induced by cues persisted over several weeks after withdrawal, and the responding was not easily extinguished after 4 weeks withdrawal. A single injection of heroin (250 micro g/kg) enhanced the responding at early stage of withdrawal, but a low dose of heroin (50, 250 micro g/kg) suppressed the responding induced by contextual or conditioned cues at 4 weeks of withdrawal. The results suggest that prolonged withdrawal may increase the risk of relapse to heroin seeking.