A RODENT MODEL FOR CHRONIC METHAMPHETAMINE TOXICITY

慢性甲基苯丙胺中毒的啮齿动物模型

• 批准号: 6289624
• 负责人: ALANE S KIMES
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6289624
• 关键词: brain metabolism; chronic disease /disorder; cognition disorders; cytotoxicity; disease /disorder model; drug abuse; glucose metabolism; laboratory rat; methamphetamine; neural information processing

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. - methamphetamine, neurotoxicity, rats, drug abuse, 2-deoxy- D-[C-14]deoxyglucose method

人类受试者的慢性甲基苯丙胺滥用与神经元毒性有关，表现为认知缺陷。启动了对大鼠的研究，以建立一个模型，在该模型中可以测试毒性的时间过程、效应的可逆性和治疗方式的潜在效应。对大鼠进行长期治疗方案，该方案旨在模拟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，该方法提供了葡萄糖局部脑代谢率（rCMRglc）的定量图，这是一项脑功能指标。与对照组动物相比，慢性甲基苯丙胺在34个测定区域中的14个区域和全脑中产生较低的rCMRglc。最强的影响发生在压后皮质、尾壳核头部、丘脑腹后核。和髓核的核心接受慢性甲基苯丙胺的大鼠基础脑代谢降低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的代谢效应的广泛分布表明，这种药物的人类滥用者具有广泛的大脑缺陷，这是其认知和情感症状的基础。- 甲基苯丙胺，神经毒性，大鼠，药物滥用，2-脱氧- D-[C-14]脱氧葡萄糖法