A RODENT MODEL FOR CHRONIC METHAMPHETAMINE TOXICITY

人类受试者长期滥用甲基苯丙胺与神经毒性有关，在行为上表现为认知缺陷。开始在大鼠身上进行研究，以建立一个模型，在该模型中可以测试毒性的时程、效果的可逆性和治疗方式的潜在效果。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。用2-脱氧-D-[1-[C-14]葡萄糖(DG)方法评估脑功能的影响，该方法提供了大脑局部葡萄糖代谢率(RCMRglc)的定量地图，rCMRglc是大脑功能的指标。与对照组动物相比，慢性甲基苯丙胺在34个区域中的14个区域和整个大脑中产生了较低的rCMRglc。最强烈的影响出现在脾后皮质、尾壳核头、丘脑腹后核和伏核核心。慢性服用甲基苯丙胺的大鼠基础脑代谢降低可能反映了长期使用该药物的毒性效应。甲基苯丙胺在大鼠大脑中代谢作用的广泛分布表明，滥用这种药物的人有广泛的大脑缺陷，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.