Differential effects of donepezil on methamphetamine and cocaine dependencies
Differential effects of donepezil on methamphetamine and cocaine dependencies
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DOI：
10.1196/annals.1369.042
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Ikeda, Kazutaka
中科院分区：
文献类型：
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作者：
Takamatsu, Yuk;Yamanishi, Yoshiharu;Ikeda, Kazutaka
多奈哌齐是一种胆碱酯酶抑制剂，已广泛用作治疗阿尔茨海默病的药物。最近，一项研究表明，多奈哌齐可抑制可卡因引起的成瘾行为，包括可卡因条件性位置偏爱（CPP）和对可卡因的运动过敏。在本研究中，我们研究了多奈哌齐对甲基苯丙胺 (METH) 诱导的小鼠行为变化的影响。在平衡 CPP 试验中，在腹膜内 (i.p.) 腹膜内 (i.p.) 施用 3 mg/kg 多奈哌齐，然后再腹腔注射 2 mg/kg 冰毒。未能抑制 METH CPP，而用 3 mg/kg 多奈哌齐预处理可消除可卡因的 CPP（10 mg/kg，腹膜内注射）。同样，在运动敏化实验中，腹膜内注射。在腹腔注射 2 mg/kg 冰毒之前给予 1 mg/kg 多奈哌齐。未能抑制对冰毒的运动敏感性，而用 1 mg/kg 多奈哌齐预处理可显着抑制对可卡因的运动敏感性（10 mg/kg，腹膜内注射）。这些结果表明，多奈哌齐可能是治疗可卡因依赖的有用工具，但不适用于治疗冰毒依赖。多奈哌齐对冰毒和可卡因引起的成瘾行为的影响差异可能是由于乙酰胆碱在冰毒和可卡因依赖性机制中的参与程度不同所致。
Donepezil, a choline esterase inhibitor, has been widely used as a medicine for Alzheimer's disease. Recently, a study showed that donepezil inhibited addictive behaviors induced by cocaine, including cocaine-conditioned place preference (CPP) and locomotor sensitization to cocaine. In the present study, we investigated the effects of donepezil on methamphetamine (METH)-induced behavioral changes in mice. In counterbalanced CPP tests, the intraperitoneal (i.p.) administration of 3 mg/kg donepezil prior to 2 mg/kg METH i.p. failed to inhibit METH CPP, whereas pretreatment with 3 mg/kg donepezil abolished the CPP for cocaine (10 mg/kg, i.p.). Similarly, in locomotor sensitization experiments, i.p. administration of 1 mg/kg donepezil prior to 2 mg/kg METH i.p. failed to inhibit locomotor sensitivity to METH, whereas pretreatment with 1 mg/kg donepezil significantly inhibited locomotor sensitivity to cocaine (10 mg/kg, i.p.). These results suggest that donepezil may be a useful tool for treating cocaine dependence but not for treating METH dependence. The differences in the donepezil effects on addictive behaviors induced by METH and cocaine might be due to differences in the involvement off acetylcholine in the mechanisms of METH and cocaine dependencies.