PSYCHOSTIMULANTS AND LENTIVIRAL INFECTION OF NEURAL CELL

甲基苯丙胺（冰毒）是一种情绪提升，积极加强药物对人类的高滥用潜力。持续使用甲基苯丙胺会导致一系列不良的心理、免疫和永久性的神经毒理学效应。不同物种对神经毒理学效应的敏感性不同，但在皮层下结构的5 -羟色胺能和多巴胺能神经末梢变性方面是一致的。全世界已知有越来越多的艾滋病毒-1感染者滥用冰毒。慢性甲基苯丙胺滥用和HIV-1感染的协同效应目前尚不清楚。这两种情况对免疫系统都有不利的影响，并导致进行性、皮层下介导的神经变性。猫是一个非常适合的动物模型来研究慢性甲基安非他明滥用和HIV-1感染的协同效应。猫对冰毒的代谢和敏感性与人类相似。此外，神经艾滋病的猫模型有充分的文献记载，在猫免疫缺陷病毒（FIV）感染后，导致进行性、皮层下介导的神经变性，并伴有免疫缺陷、行为障碍和神经元丧失。因此，本研究的总体目的是评估FIV感染和慢性冰毒伴急性“狂欢”对免疫功能和病毒相互作用、神经行为和神经生理以及神经变性的协同作用。总的假设是FIV和冰毒在增强病毒载量、免疫抑制、行为改变和随后的神经退行性变方面具有协同作用。将研究三个具体目标：1。测定FIV感染猫在6个月内给药前后的药代动力学模式、免疫功能和病毒载量；2. 确定2年期间未感染和FIV感染猫慢性给药的行为、生理和神经化学神经毒性；和3。确定甲基安非他明和FIV对谷氨酸摄取、释放和谷氨酸代谢的相互作用与基底节区兴奋性毒性神经元丢失有关。目的是阐明甲基苯丙胺和HIV-1相互作用的作用和机制。

Methamphetamne (METH) is a mood-elevating, positively reinforcing drug of high abuse potential in humans. Continuous use of METH can lead to a number of adverse psychological, immunological, and permanent neurotoxicological effects. Species sensitivity to the neurotoxicological effects vary, but are uniform in creating degeneration of serotonergic and dopaminergic nerve terminals of subcortical structures. Increasingly greater numbers of HIV-1 infected individuals are known METH abusers throughout the world. The synergistic effects of chronic METH abuse and HIV-1 infection are presently poorly understood. Both conditions have detrimental affects on the immune system and cause a progressive, subcortical mediated neurodegeneration. The cat is a well-suited animal model to study the synergistic effects of chronic METH abuse and HIV-1 infection. Cats exhibit a similar metabolism of and sensitivity to METH as humans. Moreover, a feline model of neuroAIDS is well-documented, resulting in a progressive, subcortical mediated neurodegeneration associated with immunodeficiency, behavioral disturbances, and neuronal loss after feline immunodeficiency virus (FIV) infection. Thus, the overall objective of this study is to evaluate the synergistic effects of FIV infection and chronic METH with acute "binges" on immune function and viral interaction, neurobehavior and neurophysiology, and neurodegeneration. The overall hypothesis is that FIV and METH are synergistic in enhancing viral load, immunosuppression, altered behavior, and subsequent neurodegeneration. Three specific aims will be studied: 1. Determine the pharmacokinetics patterns, immune function and viral load prior to and after METH administration to FIV infected cats over a 6 month period; 2. Determine the behavioral, physiologic, and neurochemical neurotoxicity of chronic METH administration in uninfected and FIV infected cats over a 2 year period; and 3. Determine the interaction of METH and FIV on glutamate uptake, release, and glutatmate metabolism as related to excitotoxic neuronal loss in the basal ganglia. The goal is to elucidate on the effects and mechanisms of METH and HIV-1 interaction.