| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2493846 | Neuropharmacology | 2012 | 7 Pages |
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 Galantamine at those doses failed to alter the locomotor activity in heroin-withdrawn rats.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.
