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

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• 作者：Huifen Liu ; Miaojun Lai ; Xin Zhou ; Huaqiang Zhu ; Yu Liu ; Anna Sun ; Baomiao Ma ; Fuqiang Zhang ; Wenhua Zhou ; ^{whzhou@vip.163.com}
• 关键词：Acetylcholine ; Muscarinic ; Nicotinic receptor ; Opioid receptor ; Self-administration
• 刊名：Neuropharmacology
• 出版年：2012
• 期刊代码：33_00283908
• 类别：pha
• 出版时间：June, 2012
• 卷：62
• 期：8
• 页码：2515-2521
• 文件大小：337 K

摘要

Background and objective

Evidence 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.

Methods

Rats 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.

Results

The 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 Galantamine at those doses failed to alter the locomotor activity in heroin-withdrawn rats.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.

Conclusion

The 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.