A RODENT MODEL FOR CHRONIC METHAMPHETAMINE TOXICITY

慢性甲基苯丙胺滥用与神经毒性有关，表现为认知缺陷。在大鼠身上进行研究，以建立模型，测试其毒性的时间过程、作用的可逆性和治疗方式的潜在效应。老鼠接受了一种慢性治疗方案，该方案旨在模仿人类甲基苯丙胺滥用者自我给药的方式。使用2-脱氧-d -[1-[C-14]]葡萄糖（DG）方法评估脑功能的影响，该方法提供了区域脑葡萄糖代谢率（rCMRglc）的定量图，这是脑功能的指标。与对照动物相比，慢性甲基苯丙胺在34个分析区域中的14个区域和全脑产生较低的rCMRglc。最强烈的影响发生在脾后皮质、尾状壳核头部、丘脑腹后核和伏隔核核心。长期服用甲基苯丙胺的大鼠较低的基础脑代谢可能反映了长期使用这种药物的毒性作用。甲基苯丙胺在大鼠大脑中广泛分布的代谢效应表明，这种药物的人类滥用者有广泛的大脑缺陷，这是他们认知和情感症状的基础。

Chronic methamphetamine abuse in human subjects is associated with neuronal toxicity, expressed behaviorally as cognitive deficits. Studies in rats were initiated to establish a model in which the time course to toxicity, reversibility of effects and potential effects of treatment modalities could be tested. Rats were subjected to a chronic treatment regimen that was designed to mimic the manner in which human methamphetamine abusers self-administer the drug. The effects of brain function were assessed using the 2-deoxy-D-[1-[C-14]]glucose (DG) method, which provides quantitative maps of regional cerebral metabolic rates for glucose (rCMRglc), an index of brain function. Compared to effects in control animals, chronic methamphetamine produced lower rCMRglc in 14 out of 34 regions assayed and in whole brain. The most robust effects occurred in the retrosplenial cortex, head of the caudate putamen, ventroposterior thalamic n. and core of the nucleus accumbens. Lower basal brain metabolism in rats receiving chronic methamphetamine may reflect the toxic effects of chronic use of this drug. The wide distribution of the metabolic effects of methamphetamine in the rat brain suggests that human abusers of this drug have extensive cerebral deficits that underlie their cognitive and emotional symptoms.