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: 7716193
• 负责人: PETER J WINSAUER
• 金额: $ 6.33万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-21 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716193
• 关键词: Acquired Immunodeficiency Syndrome; Adult; Alcohol abuse; Alcohols; Animals; Antiviral Therapy; Behavioral; Brain; Chronic; Complex; Computer Retrieval of Information on Scientific Projects Database; Dementia; Diagnosis; Effectiveness; Enrollment; Ethanol; Funding; Grant; HIV; Impaired cognition; Infection; Institution; Macaca mulatta; Measurement; Monkeys; N-Methyl-D-Aspartate Receptors; NMDA receptor antagonist; Neurologic; Neurons; Neuropsychological Tests; Pharmaceutical Preparations; Procedures; Rate; Research; Research Personnel; Resources; Role; SIV; Saline; Site; Source; Sucrose; Testing; United States National Institutes of Health; Virus Diseases; Week; alcohol effect; behavior test; cohort; day; frontal lobe; neuron loss; neuropsychological; research study

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. Two cohorts of 8 animals were originally enrolled on this study. Of the first cohort, all 4 SIV-innoculated animals succumbed to infection and only the 4 saline-innoculated subjects remain: 2 alcohol treated and 2 sucrose treated. Regarding the second cohort, 7 animals are undergoing pre-innoculation neuropsychological testing with drug challenge with concomitant sucrose (3) or alcohol (4) administration over 4 consecutive days each week. One subject in the second cohort succumbed to unknown causes unrelated to the study.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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学特征，包括额叶皮层神经元的损失。 50-75% 的 HIV 感染成年人被诊断患有神经系统问题，20% 的人患有获得性免疫缺陷综合症 (AIDS) 痴呆症。 酗酒和艾滋病毒感染也会对异常的大脑电生理测量产生附加影响。 然而，酒精影响与艾滋病相关神经元和认知功能障碍之间的关系需要进一步研究。 拟议的研究将检验总体假设，即酒精会揭示感染猿免疫缺陷病毒（SIV）的恒河猴的神经心理缺陷。 该部分将系统地探索上一个资助期间的行为测试期间乙醇和 SIV 之间发生的重要相互作用，并开始研究 GABAA 和 NMDA 受体在该相互作用中的潜在作用。 这些实验将研究长期饮酒是否会：1）在复杂的神经心理学程序（例如重复获取）下，增强 SIV 在猴子中产生的神经心理缺陷，2）产生对酒精的速率降低和错误增加效应的耐受性以及对酒精的交叉耐受性。三种不同的、位点特异性的、正 GABAA 调节剂在假接种和 SIV 接种的猴子中的行为效应，3) 对 NMDA 受体拮抗剂的行为效应产生交叉耐受假接种或 SIV 接种的猴子，4) 降低 SIV 感染猴子的抗病毒治疗效果。 本研究最初招募了两组 8 只动物。 在第一组中，所有 4 只接种 SIV 的动物均死于感染，仅剩下 4 只接种盐水的受试者：2 只接受酒精治疗，2 只接受蔗糖治疗。 关于第二组，7 只动物正在接受接种前神经心理学测试，每周连续 4 天同时给予蔗糖 (3) 或酒精 (4) 药物挑战。 第二组中的一名受试者死于与研究无关的未知原因。