AIDS & DRUG Abuse: Tremor and motor control in macaques

艾滋病

• 批准号: 6656697
• 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/6656697
• 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造成的。因此，了解药物滥用对艾滋病的影响仍然是艾滋病中枢神经系统病理学的一个重要目标，许多滥用的药物，例如精神运动兴奋剂，都涉及神经递质多巴胺（DA）。可以预见的是，由于 DA 损伤，艾滋病患者也会出现运动障碍。由于 DA 病理学相同，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。开发对中枢神经系统损伤敏感的行为测试对于我们理解艾滋病引起的中枢神经系统病理背后的机制至关重要。在疾病进展的早期证明损害对于确定哪些中枢神经系统变化导致与艾滋病相关的中枢神经系统功能障碍以及导致功能障碍的机制是必要的。运动损伤已被证明是艾滋病中枢神经系统损伤（包括认知功能损伤）的可靠标志。该提案将开发新程序，并将其纳入正在进行的关于猕猴艾滋病和滥用药物的研究中。将开发一种运动测试，同时测量精细运动控制的行为和生理测量。该测试称为“力和微震颤”测试，将评估动物调节按压杆的力量的能力。当猴子按压杆时，还将测量生理震颤。将研究每次按压需要多大的力以及猴子应保持按压多长时间的参数，以确定测量微震的最佳方法。 DA 参与 AIDS 和许多滥用药物的 CNS 病理学，这使得了解 DA 操作对这项任务的影响变得重要。DA 功能的增加和减少将分别使用可卡因和 DAD 1 和 D2 受体拮抗剂的预处理来评估。一旦参数确定，该任务将在随后感染 SIV 的猴子中进行训练，并评估该任务对 SIV 引起的运动障碍的敏感性。本提案中开发的行为测试将成为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，特别是研究精神运动兴奋剂和其他可能损害中枢神经系统多巴胺能系统的药物。