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; 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。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。酒精和人类免疫缺陷病毒（HIV）感染已显示出产生相似的神经病理学特征，包括额叶皮质中神经元的丧失。此外，有50-75％的HIV感染成人被诊断出患有神经系统疾病，20％的人患有可获得的免疫缺陷综合征（AIDS）痴呆症。还有实验证据表明，慢性酒精消耗增强了与AIDS相关的神经病。例如，长期滥用酒精的艾滋病毒阳性患者通常具有更大的神经系统缺陷，据报道，慢性酒精滥用在HIV过程中会产生异常。酒精滥用和HIV感染也对异常的脑电生理测量具有添加剂作用。但是，酒精的影响与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检查。提出的研究将检验总体假设，即酒精揭示了感染了邻氨酸免疫缺陷病毒（SIV）的恒河猴的神经心理缺陷。该组件将系统地探索前一个资金期间行为测试期间乙醇和SIV之间发生的显着相互作用，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和使用SIV的方案，这将控制感染受试者的乙醇消耗，同时避免许多经常与人类损害临床研究的不受控制的变量。 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）产生对NMDA受体拮抗剂在假猴或SIV接种猴子中的行为影响的交叉耐受性，4）降低抗病毒治疗在SIV感染的猴子中的有效性。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学测试，每周进行4次饮酒。其余的八只动物是新获取的，并正在为神经心理学测试提供条件。目前，所有16只动物都是Niave，尚未感染