Galantamine attenuates the heroin seeking behaviors induced by cues after prolonged withdrawal in rats

Background and objectiveEvidence shows that acetylcholinergic transmission in the ventral tegmental area (VTA) or nucleus accumbens (NAc) plays an important role in heroin-seeking induced by cues. Cholinergic modulation of VTA neurons arises from the lateral dorsal tegmental nucleus (LDT). The present studies investigated the effect of systemic or intra- LDT administration of galantamine, an inhibitor of acetylcholinesterase, on heroin-seeking induced by cues.MethodsRats were trained to self-administer heroin for 12 days, underwent extinction training for 12 days followed by two weeks in their home cages. Then the conditioned cues were introduced for the reinstatement of heroin-seeking.ResultsThe reinstatement of heroin-seeking induced by cues was attenuated by the administration of galantamine (0, 0.3, 1 or 3 mg/kg, i.p.) in a dose-dependent manner. In contrast, galantamine only at the dose of 3 mg/kg could inhibit the reinstatement of sucrose-seeking. Galantamine at those doses failed to alter the locomotor activity in heroin-withdrawn rats. The inhibition of drug-seeking by galantamine was reversed by pretreatment with scopolamine (0.5 mg/kg) but not with mecamylamine (3 mg/kg) or scopolamine methobromide (1 mg/kg). Moreover, the microinjection of galantamine into the LDT blocked cue-induced heroin-seeking, while the microinjection of scopolamine into the LDT reversed the inhibitory effect of galantamine on drug-seeking behavior.ConclusionThe results suggest that cholinergic transmission in the LDT may play a critical role in heroin-seeking behavior induced by cues and that galantamine may have the beneficial effect of blocking heroin-seeking behavior, which is mediated through its actions on the muscarinic receptors.

► We identified galantamine’s ability to inhibit heroin-seeking behavior.
► The inhibitory action of galantamine is reversed by scopolamine, but not by mecamylamine.
► Microinjection of galantamine into the LDT decreases heroin-seeking behavior.
► Scopolamine reverses the inhibitory action of galantamine in the LDT.