ALCOHOL AND HIV INFECTION: ADDITIVE NEUROPHYSCHOLOGICAL EFFECTS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。酒精和人类免疫缺陷病毒(HIV)感染已被证明会产生类似的神经病理特征，包括额叶皮质神经元的丧失。此外，50%-75%的艾滋病毒感染者被诊断为神经系统问题，20%的人患上获得性免疫缺陷综合症(艾滋病)痴呆症。也有实验证据表明，长期饮酒会加剧艾滋病相关的神经病变。例如，长期酗酒的艾滋病毒阳性患者通常有更大的神经缺陷，据报道，长期酗酒会在艾滋病毒过程的早期产生异常。酗酒和HIV感染对异常的脑电生理测量也有相加的影响。然而，酒精和艾滋病相关的神经元和认知功能障碍之间的影响之间的关系还需要进一步研究。拟议中的研究将检验酒精暴露了感染了猴免疫缺陷病毒(SIV)的恒河猴神经心理缺陷的总体假设。这一部分将系统地探索乙醇和SIV之间在上一个资助期的行为测试中发生的重要相互作用，并开始研究GABAA和NMDA受体在这种相互作用中的潜在作用。这项研究的一个重要方面将是乙醇给药方案和SIV的使用，这将控制感染对象的乙醇摄入量，同时避免许多经常危及临床研究与人类的不可控变量。这些实验将探讨长期饮酒是否会1)加强SIV在复杂的神经心理程序(如重复获得)下产生的神经心理缺陷，2)在假接种和SIV接种的猴子中对酒精的减速和错误增加效应产生耐受性，以及对三种不同的、部位特异的、阳性的GABAA调节剂的行为效应产生交叉耐受性，3)在假接种或SIV接种的猴子中产生对NMDA受体拮抗剂的行为效应的交叉耐受性，以及4)在SIV感染的猴子中降低抗病毒治疗的有效性。目前有16只动物参加了这项研究。其中八只动物正在接受神经心理测试，每周四次饮酒。剩下的八只动物是新获得的，正在接受神经心理测试。目前所有的16只动物都是新生的，还没有感染过

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alcohol and Human Immunodeficiency Virus (HIV) infection have been shown to produce similar neuropathological profiles, including loss of neurons in the frontal cortex. Additionally, 50-75% of HIV-infected adults are diagnosed with neurological problems, and 20% develop Acquired Immunodeficiency Syndrome (AIDS) dementia. There is also experimental evidence indicating that chronic alcohol consumption potentiates AIDS-related neuropathy. For example, HIV-positive patients who are long-term abusers of alcohol generally have greater neurologic deficits, and chronic alcohol abuse has been reported to produce abnormalities earlier in the HIV process. Alcohol abuse and HIV infection also have additive effects on abnormal brain electrophysiological measurements. However, the relationship between the effects of alcohol and AIDS-related neuronal and cognitive dysfunction require further examination. The studies proposed will test the overall hypothesis that alcohol unmasks neuropsychological deficits in rhesus monkeys infected with simian immunodeficiency virus (SIV). This component will systematically explore the significant interaction that occurred between ethanol and SIV during behavioral testing in the previous funding period and begin to examine the potential role of GABAA and NMDA receptors in that interaction. An important aspect of this research will be the regimen for ethanol administration and the use of SIV, which will control for ethanol consumption in infected subjects while avoiding many uncontrolled variables that frequently compromise clinical studies with humans. These experiments will investigate whether chronic alcohol administration will 1) potentiate neuropsychological deficits produced by SIV in monkeys responding under a complex neuropsychological procedure such as repeated acquisition, 2) produce tolerance to the rate-decreasing and error-increasing effects of alcohol and cross tolerance to behavioral effects of three different, site-specific, positive GABAA modulators in both sham- and SIV-inoculated monkeys, 3) produce cross tolerance to behavioral effects of NMDA receptor antagonists in both sham- or SIV-inoculated monkeys, and 4) reduce effectiveness of antiviral therapy in SIV-infected monkeys. There are currently 16 animals enrolled on this study. Eight of the animals are undergoing neuropsychological testing and are administered alcohol 4 times weekly. The remaining eight animals are newly acquired and are being conditioned for the neuropsychological testing. Currently all 16 of the animals are niave, have not been infected with