PSYCHOSTIMULANTS AND LENTIVIRAL INFECTION OF NEURAL CELL

甲基苯丙胺(甲基苯丙胺)是一种提升情绪、积极强化的药物，在人体内具有很高的滥用潜力。持续使用冰毒会导致一些不良的心理、免疫和永久性神经毒理影响。不同物种对神经毒理效应的敏感性不同，但在造成皮质下结构的5-羟色胺能和多巴胺能神经末梢退化方面是一致的。全世界越来越多的HIV-1感染者是已知的冰毒滥用者。目前对长期滥用冰毒和艾滋病毒-1感染的协同效应知之甚少。这两种情况对免疫系统都有不利影响，并导致进行性皮质下介导的神经变性。猫是研究慢性冰毒滥用和HIV-1感染的协同效应的非常合适的动物模型。猫表现出与人类相似的冰毒新陈代谢和敏感性。此外，猫的神经艾滋病模型被很好地记录下来，导致进行性的皮质下介导的神经变性，与免疫缺陷、行为障碍和猫免疫缺陷病毒(FIV)感染后的神经元丢失相关。因此，这项研究的总体目标是评估FIV感染和慢性冰毒与急性“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退变的协同影响。总体假设是，FIV和冰毒在增强病毒载量、免疫抑制、改变行为和随后的神经退化方面具有协同作用。我们将研究三个具体目标：1.在6个月的时间里，确定给感染FIV的猫注射冰毒前后的药代动力学模式、免疫功能和病毒载量；2.确定长期服用冰毒对未感染和感染FIV的猫的行为、生理和神经化学毒性；以及3.确定冰毒和FIV对谷氨酸摄取、释放和谷氨酸代谢的交互作用，以及与基底节兴奋性毒性神经元丢失有关的谷氨酸代谢。目的是阐明冰毒和HIV-1相互作用的效果和机制。

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.