Rationale:Accumulating evidence suggests that cholinergic systems modulate dopaminergic function in brain pathways thought to mediate heroin’s abuse-related effects. Objectives:This study investigated whether huperzi...
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Rationale:Accumulating evidence suggests that cholinergic systems modulate dopaminergic function in brain pathways thought to mediate heroin’s abuse-related effects. Objectives:This study investigated whether huperzine A,a natural acetylcholinesterase inhibitor,has beneficial effects on the heroin seeking induced by cue or heroin after extinction from heroin self-administration in rats. The experiments were also to examine a potential role for the laterodorsal tegmental nucleus(LDT)/ pedunculpontine tegmental nucleus(PPTg) in the reinstatement of heroin seeking. Methods:Rats were trained to self-administer heroin (50 μg·kg-1 per infusion ; FR1) for 14 days,A progressive ratio schedule (PR3-4) was used to evaluate the relative motivational value of heroin reinforcement,and the reinstatement model of drug seeking was used to determine whether huperzine A treatment inhibited cue-and heroin-induced drug-seeking,we also assessed the effect of administration of huperzine A into the LDT/PPTg on heroin-seeking triggered by heroin-paired cues. Results:Pretreatment with huperzine A dose dependently reduced responding for heroin under both the FR1 and PR schedule. Moreover,acute treatment with huperzine A at dose from 50 to 200 μg·kg-1 potently suppressed the cue-and heroin-induced reinstatement of heroin-seeking behavior following extinction. Additionally,intracranial infusion of huperzine A(1.0-3.0 μg/side),into the LDT/PPTg potently and dose dependently attenuated heroin-seeking in response to cue presentations. Conclusion:These results add to a growing literature indicating that acetylcholinesterase inhibitor attenuates the reinstatement of heroin seeking. Importantly,the current findings also indicate that cholinergic activities in LDT/PPTg might play an important role in mediating cue-induced reinstatement of heroin seeking.
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