Alcohol & HIV Infection-Additive Neuropsychologic Effect

酒精和人类免疫缺陷病毒(HIV)感染被证明会产生类似的结果 神经病理特征，包括额叶皮质神经元的丢失。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仍然知之甚少，需要进一步研究。本研究部分提出的研究将检验总体假设，即 酒精暴露感染猿猴的神经心理缺陷 免疫缺陷病毒(SIV)。更具体地说，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期间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。特别是，这些实验将考察长期饮酒是否会1)加强SIV对猴子在复杂的神经心理程序(如重复习得)下产生的神经心理缺陷，2)对酒精的减速和错误增加效应产生耐受性，以及对行为的交叉耐受性 三种不同的、部位特异的、阳性的GABAA调节剂在假接种和SIV感染的猴子中的作用；3)在假接种或SIV感染的猴子中对NMDA受体拮抗剂的行为影响产生交叉耐受性；以及4)降低SIV感染的猴子的抗病毒治疗的有效性。

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 produces 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 are still poorly understood and require further examination. The studies proposed in this research component will test the overall hypothesis that alcohol unmasks neuropsychological deficits in rhesus monkeys infected with simian immunodeficiency virus (SIV). More specifically, 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. In particular, these experiments will investigate whether chronic alcohol administration will 1) potentiate the 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 the behavioral effects of three different, site-specific, positive GABAA modulators in both sham- and SIV-inoculated monkeys, 3) produce cross tolerance to the behavioral effects of NMDA receptor antagonists in both sham- or SIV-inoculated monkeys, and 4) reduce the effectiveness of antiviral therapy in SIV-infected monkeys.