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: 7562254
• 负责人: PETER J WINSAUER
• 金额: $ 7.16万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562254
• 关键词: Acquired Immunodeficiency Syndrome; Adult; Alcohol abuse; Alcohols; Animals; Antiviral Therapy; Behavioral; Brain; Catheters; Chronic; Complex; Computer Retrieval of Information on Scientific Projects Database; Dementia; Diagnosis; Effectiveness; Enrollment; Ethanol; Funding; Future; Grant; HIV; Impaired cognition; Implant; Infection; Institution; Macaca mulatta; Measurement; Monkeys; N-Methyl-D-Aspartate Receptors; NMDA receptor antagonist; Neurologic; Neurons; Neuropsychological Tests; Procedures; Rate; Research; Research Personnel; Resources; Role; SIV; Site; Source; Sucrose; Testing; Training; United States National Institutes of Health; Virus Diseases; Week; alcohol effect; behavior test; 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. 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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丧失。 50-75%的艾滋病毒感染成年人被诊断为神经系统问题，20%的人发展为获得性免疫缺陷综合征（艾滋病）痴呆。 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。 本研究最初入组了16只动物，但目前只有15只动物。 7只动物正在接受神经心理学测试，每周连续4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。 其余8只动物已接受神经心理学任务培训，并将在不久的将来植入其慢性胃内导管。