PSYCHOSTIMULANTS AND LENTIVIRAL INFECTION OF NEURAL CELL

甲基苯丙胺（METH）是一种情绪提升，积极加强药物的高滥用潜力的人类。 持续使用甲氧亚甲基可导致许多不良的心理、免疫和永久性神经毒理学影响。种属对神经毒理学效应的敏感性各不相同，但在造成皮质下结构的多巴胺能和多巴胺能神经末梢变性方面是一致的。 在全世界，已知的甲基苯丙胺滥用者中有越来越多的HIV-1感染者。目前对慢性甲基苯丙胺滥用和HIV-1感染的协同效应了解甚少。 这两种情况都对免疫系统产生有害影响，并导致进行性皮质下介导的神经变性。猫是研究慢性METH滥用和HIV-1感染的协同作用的非常合适的动物模型。 猫表现出与人类相似的代谢和敏感性。 此外，神经AIDS的猫模型被充分记录，导致猫免疫缺陷病毒（FIV）感染后与免疫缺陷、行为障碍和神经元损失相关的进行性皮质下介导的神经变性。 因此，本研究的总体目标是评估FIV感染和慢性METH与急性“狂欢”对免疫功能和病毒相互作用、神经行为和神经生理学以及神经变性的协同作用。 总体假设是FIV和METH在增强病毒载量、免疫抑制、行为改变和随后的神经变性方面具有协同作用。 三个具体目标将进行研究：1。在6个月的时间内，确定METH施用给FIV感染的猫之前和之后的药代动力学模式、免疫功能和病毒载量; 2.确定在2年时间内在未感染和FIV感染的猫中长期给予METH的行为、生理和神经化学神经毒性;和3.确定METH和FIV对谷氨酸摄取、释放和谷氨酸代谢的相互作用，这些相互作用与基底神经节中的兴奋性毒性神经元损失有关。 目的是阐明METH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.