ALCOHOL AND HIV INFECTION: ADDITIVE NEUROPHYSCHOLOGICAL EFFECTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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。50%-75%的艾滋病毒感染者被诊断为神经系统问题，20%的人患有获得性免疫缺陷综合征(艾滋病)痴呆症。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。最初有16只动物参加了这项研究，但目前只有15只。其中七只动物正在接受神经心理测试，每周连续四天给予蔗糖(3)或酒精(4)。每组(酒精或蔗糖)的两名受试者也接种了SIV，但蔗糖组的一名受试者死于感染。剩下的8只动物已经接受了神经心理学任务的训练，并将在不久的将来植入它们的慢性胃内导管。

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 has been shown to produce similar neuropathological profiles, including loss of neurons in the frontal cortex. 50-75% of HIV-infected adults are diagnosed with neurological problems, and 20% develop Acquired Immunodeficiency Syndrome (AIDS) dementia. 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 requires 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. 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. 16 animals were originally enrolled on this study, but currently there are only 15 animals. Seven of the animals are undergoing neuropsychological testing and are administered either sucrose (3) or alcohol (4) over 4 consecutive days each week. Two subjects from each group (alcohol or sucrose) were also inoculated with SIV, but one subject from the sucrose group succumbed to the infection. The remaining eight animals have been trained under the neuropsychological task and will have their chronic intragastric catheters implanted in the near future.