ALCOHOL AND HIV INFECTION: ADDITIVE NEUROPHYSCHOLOGICAL EFFECTS

酒精和艾滋病毒感染：附加的神经生理效应

• 批准号: 7348979
• 负责人: PETER J WINSAUER
• 金额: $ 6.54万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7348979
• 关键词: ALCOHOL; HIV; INFECTION; ADDITIVE; NEUROPHYSCHOLOGICAL

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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。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学特征，包括额叶皮层神经元的丧失。此外，50-75%的艾滋病毒感染成年人被诊断患有神经系统问题，20%的人发展为获得性免疫缺陷综合征（艾滋病）痴呆。也有实验证据表明，长期饮酒会增强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功能缺陷，据报道，长期酗酒会在艾滋病毒感染过程的早期产生异常。酒精滥用和HIV感染也对异常的脑电生理测量产生叠加效应。然而，酒精的影响与艾滋病相关的神经元和认知功能障碍之间的关系需要进一步研究。这项研究将检验一个总体假设，即酒精暴露了感染猴免疫缺陷病毒（SIV）的恒河猴的神经心理缺陷。这一部分将系统地探索在上一个资助期的行为测试中乙醇和SIV之间发生的显著相互作用，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，这将控制受感染受试者的乙醇消耗，同时避免许多经常影响人类临床研究的不受控制的变量。这些实验将研究长期酒精给药是否会1）在猴中增强SIV产生的神经心理学缺陷，猴在复杂的神经心理学程序如重复获得下响应，2）在假接种和SIV接种的猴中产生对酒精的速率降低和错误增加效应的耐受性和对三种不同的、位点特异性的阳性GABAA调节剂的行为效应的交叉耐受性，3）在假接种或SIV接种的猴中产生对NMDA受体拮抗剂的行为效应的交叉耐受，和4）降低抗病毒治疗在SIV感染的猴中的有效性。本研究目前入组了16只动物。其中8只动物正在接受神经心理学测试，每周给予4次酒精。其余8只动物是新获得的，正在进行神经心理学测试。目前所有16只动物均为尼阿韦，尚未感染