Abstract: Rationale: Heroin addiction is a disorder that stems from maladaptive plasticity within neural circuits and produces broad cognitive deficits. Despite considerable advances in psychotherapy and pharmacotherapy for heroin addiction, but there are a few treatments for the heroin relapse after long term abstinence. Preclinical and clinical evidence indicates that the cognitive deficit during the addiction and withdrawal process, thus, cognitive enhancers may be used to treatment for heroin addiction. Objectives: The purpose of this study was to evaluate whether the cognitive enhancers would reduce the heroin relapse induced by cues which was associated with heroin reward or heroin priming in rat. Methods: Rats were trained to self-administer heroin under fixed ratio 1 schedule for two weeks and extinguished for 10 days, then the reinstatement of drug seeking induced by conditioned cues or heroin priming (250 µg/kg, sc) was used. Results: We evaluated systemically the effects of acetylcholinase inhibitor, PDE4 inhibitor, mGlu2/3 agonist or mGlu1/5 antagonist, etc on heroin relapse. The data showed that pretreatment with acetylcholinase inhibitor, PDE4 inhibitor, mGlu2/3 agonist or mGlu1/5 antagonist could inhibit the heroin relapse induced by cues or heroin priming in a dose-dependent manner. Meanwhile, we also illustrated the circuits and signal pathway of these compounds. Conclusion: The data demonstrated that Cognitive enhancers could be used as the   pharmacological treatments for heroin relapse or addiction.

Key words: cognitive function, heroin addiction, neuroplasticity, acetylcholine