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艾滋病中重要的目标中枢神经系统病理，许多滥用药物（例如心理刺激剂）涉及神经递质多巴胺（DA）。可以预见的是，由于具有共同的DA病理，艾滋病中也有运动障碍，当艾滋病和药物滥用合并时，运动行为可能会双重攻击。对CNS损害敏感的行为测试的发展对于我们对艾滋病产生的中枢神经系统病理背后的机制的理解至关重要。为了确定哪些CNS变化导致与艾滋病相关的中枢神经系统功能障碍以及哪些机制导致功能障碍，因此必须在疾病进展中证明损伤。运动障碍已被证明是艾滋病中CNS损伤的可靠标记，包括认知功能的损害。该提案将制定新程序，并将其纳入正在进行的有关艾滋病和滥用毒品的研究中。将开发出同时测量精细运动控制的行为和生理测量的运动测试。该测试是“力和微晶体测试”测试，将评估动物调节杆生理震颤的力量的能力，同时猴子按下杆子。每次压力都应需要多少力的参数，以及必须研究猴子必须维持压力的时间，以确定测量微型转速的最佳方法。 DA参与艾滋病和许多滥用药物的中枢神经系统病理学，使得DA操纵对此任务的影响很重要，而DA功能的降低将分别使用可卡因和DAD 1和D2受体拮抗剂的预处理进行评估。一旦建立了参数，将在后来感染SIV的猴子中对任务进行训练，并将评估任务对SIV引起的运动障碍的敏感性。在本提案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，尤其是对心理兴奋剂和其他有可能损害CNS多巴胺能系统损害的药物的研究。