AIDS & DRUG Abuse: Tremor and motor control in macaques

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滥用药物造成的。因此，了解药物滥用对艾滋病的影响仍然是艾滋病的中枢神经系统病理学的重要目标，许多滥用药物，如精神运动兴奋剂，涉及神经递质多巴胺（DA）。可以预见的是，由于共同的DA病理，当艾滋病和药物滥用合并时，运动行为可能会受到双重攻击。对中枢神经系统损伤敏感的行为测试的发展对我们理解艾滋病引起中枢神经系统病理的机制至关重要。在疾病进展的早期证明损害是必要的，以确定哪些CNS变化导致与艾滋病相关的CNS功能障碍，以及什么机制导致功能障碍。运动障碍已被证明是艾滋病患者中枢神经系统损伤的可靠标志，包括认知功能损伤。这项提议将开发新的程序，并将其纳入正在进行的关于艾滋病和猕猴滥用药物的研究中。将开发一种同时测量精细运动控制的行为和生理测量的运动测试。这项名为“力与微颤”的测试将评估动物调节按杆时力的大小的能力，同时还将测量猴子按杆时的生理震颤。为了确定测量微震动的最佳方法，研究人员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。DA参与了艾滋病和许多滥用药物的中枢神经系统病理，因此了解DA操作对这一任务的影响非常重要。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诱导的运动损伤的敏感性。本方案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。

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.