AIDS & DRUG Abuse: Tremor and motor control in macaques

艾滋病

• 批准号: 6753572
• 负责人: MICHAEL R WEED
• 金额: $ 8.18万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6753572
• 关键词: AIDS; AIDS /HIV neuropathy; Macaca nemestrina; behavior test; cocaine; disease /disorder model; dopamine; dopamine antagonists; dopamine receptor; drug abuse; neurotoxicology; pathologic process; performance; psychomotor function; simian immunodeficiency virus; technology /technique development; tremor

DESCRIPTION (provided by applicant): Approximately one third of new HIV infections occur as a consequence of drug abuse. Therefore, understanding the effects of drug abuse on AIDS remains an important goal CNS pathology in AIDS and many abused drugs, such as psychomotor stimulants, involve the neurotransmitter dopamine (DA). Predictibly, with DA insult there are also motor impairments in AIDS Because of the shared DA pathology, motor behaviors are likely to be doubly assaulted when AIDS and drug abuse are combined. The development of behavioral tests that are sensitive to CNS impairment is crucial to our understanding of the mechanisms behind the CNS pathology produced by AIDS. Demonstrating impairment earlier in the disease progression is necessary to identify which CNS changes are responsible for the CNS dysfunction associated with AIDS, and what mechanisms cause the dysfunction. Motor impairment has been shown to be a reliable marker for CNS impairment in AIDS, including impairment in cognitive function. This proposal will develop new procedures that will be incorporated into ongoing research on AIDS and abused drugs in macaques. A motor test that will simultaneously measure both behavioral and physiologic measures of fine motor control will be developed. This test, the "force and micro-tremor" test, will assess an animal's ability to regulate the amount of force with which it presses a rod Physiologic tremor will also be measured while the monkey presses the rod. Parameters of how much force should be required for each press, and how long the monkey should have to maintain the press will be investigated to determine the best method of measuring micro-tremor. The involvement of DA in the CNS pathology of both AIDS and many abused drugs makes understanding the effects of DA manipulations on this task important Increases and decreases in DA function will be assessed using pretreatments of cocaine and DAD 1 and D2 receptor antagonists, respectively. Once the parameters are established, the task will be trained in monkeys later infected with SIV, and the sensitivity of the task to SIV-induced motor impairment will be evaluated. The behavioral test developed in this proposal will be an important tool in our research on cognitive and motor consequences of AIDS and drug abuse, especially research on psychomotor stimulants and other drugs that have potential for damage to CNS dopaminergic systems.

描述（由申请人提供）：大约三分之一的新艾滋病毒感染是由于药物滥用而发生的。因此，了解药物滥用对艾滋病的影响仍然是一个重要的目标，在艾滋病和许多滥用药物，如精神兴奋剂，涉及神经递质多巴胺（DA）的CNS病理。可以预见的是，随着DA的损害，艾滋病患者也会出现运动障碍。由于共同的DA病理学，当艾滋病和药物滥用结合在一起时，运动行为可能会受到双重攻击。发展对中枢神经系统损伤敏感的行为测试对我们理解艾滋病引起的中枢神经系统病理学机制至关重要。在疾病进展的早期证明损害是必要的，以确定哪些CNS变化是与AIDS相关的CNS功能障碍的原因，以及什么机制导致功能障碍。运动障碍已被证明是AIDS患者CNS障碍（包括认知功能障碍）的可靠标志物。这项提案将开发新的程序，将纳入正在进行的关于艾滋病和猕猴滥用药物的研究。将开发一种运动测试，该测试将同时测量精细运动控制的行为和生理测量。这个测试，“力和微震颤”测试，将评估动物的能力，以调节的力量，它按下一个杆生理震颤也将被测量，而猴子按下杆。将研究每次按压需要多大的力以及猴子应该保持按压多长时间的参数，以确定测量微震颤的最佳方法。DA在AIDS和许多滥用药物的CNS病理学中的参与使得理解DA操作对这项任务的影响变得重要。将分别使用可卡因和DAD 1和D2受体拮抗剂预处理来评估DA功能的增加和减少。一旦建立了参数，将在后来感染SIV的猴子中训练该任务，并评估该任务对SIV诱导的运动障碍的敏感性。在这项提议中开发的行为测试将是我们研究艾滋病和药物滥用的认知和运动后果的重要工具，特别是对精神兴奋剂和其他可能损害CNS多巴胺能系统的药物的研究。