Kish S J, Kalasinsky K S, Furukawa Y, Guttman M, Ang L, Li L, Adams V, Reiber G, Anthony R A, Anderson W, Smialek J, DiStefano L
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Mol Psychiatry. 1999 Jan;4(1):26-32. doi: 10.1038/sj.mp.4000462.
Cognitive impairment has been reported in some chronic users of psychostimulants, raising the possibility that long-term drug exposure might damage brain neuronal systems, including the cholinergic system, which are responsible for normal cognition. We measured the activity of choline acetyltransferase (ChAT), the marker enzyme for cholinergic neurones, in autopsied brain of chronic users of cocaine, methamphetamine, and, for comparison, heroin. As compared with the controls, mean ChAT levels were normal in all cortical and subcortical brain areas examined. However, the two of 12 methamphetamine users, who had the highest brain/blood drug levels at autopsy, had a severe (up to 94%) depletion of ChAT activity in cerebral cortex, striatum, and thalamus. Based on the subjects examined in the present study, our neurochemical data suggest that brain cholinergic neurone damage is unlikely to be a typical feature of chronic use of cocaine, methamphetamine, or heroin, but that exposure to very high doses of methamphetamine could impair, at least acutely, cognitive function requiring a normal nucleus basalis cholinergic neuronal system. Reduced brain ChAT might be explained in part by a hyperthermia-related mechanism as low ChAT levels have also been observed in brain of some patients with neuroleptic drug-associated hyperthermia. Studies of cognitive and brain cholinergic status in high dose users of MA are warranted.
据报道，一些长期使用精神兴奋剂的人存在认知障碍，这增加了长期药物暴露可能损害大脑神经元系统的可能性，包括负责正常认知的胆碱能系统。我们测量了可卡因、甲基苯丙胺长期使用者以及作为对照的海洛因使用者尸检大脑中胆碱能神经元的标记酶胆碱乙酰转移酶（ChAT）的活性。与对照组相比，所有检查的皮质和皮质下脑区的ChAT平均水平均正常。然而，12名甲基苯丙胺使用者中有2人在尸检时脑/血药物水平最高，其大脑皮质、纹状体和丘脑的ChAT活性严重降低（高达94%）。基于本研究中检查的受试者，我们的神经化学数据表明，脑胆碱能神经元损伤不太可能是长期使用可卡因、甲基苯丙胺或海洛因的典型特征，但暴露于非常高剂量的甲基苯丙胺可能至少急性损害需要正常基底核胆碱能神经元系统的认知功能。脑ChAT降低可能部分由与体温过高相关的机制解释，因为在一些与抗精神病药物相关的体温过高患者的大脑中也观察到ChAT水平较低。有必要对高剂量甲基苯丙胺使用者的认知和脑胆碱能状态进行研究。
