BRAIN MONOAMINES, DRUGS AND CONDITIONED BEHAVIOR

大脑单胺、药物和条件行为

• 批准号: 2241788
• 负责人: LEWIS S SEIDEN
• 金额: $ 10.08万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2241788
• 关键词: 3,4 methylenedioxyamphetamine; 3,4 methylenedioxymethamphetamine; NMDA receptors; anorexic agent; antidepressants; behavior; behavior test; central nervous system stimulants; chordate locomotion; cocaine; depression; dopamine; eating; gamma aminobutyrate; guinea pigs; laboratory rat; methamphetamine; microdialysis; neurochemistry; neurotoxins; neurotransmitter metabolism; norepinephrine; operant conditionings; psychopharmacology; psychotomimetic drug; second messengers; serotonin; water drinking behavior

The long-range aim of the proposed research is to understand the role central nervous system neurotransmitter systems play in the mediation of the actions of psychotropic drugs and in the maintenance of behavior. Experimental work over the past several years has suggested that, as neurotransmitters in the central nervous system are modified by drugs, behavior is modified, and further, that both behavior and the environment also have an effect on neurotransmitter function. Hence, an interactive state exists between the brain, neurotransmitters and drugs on the one hand and the environment, behavior and neurotransmitters on the other. It is within this conceptual framework that we will pursue specific research projects in the coming years. We will focus on dopamine, norepinephrine, 5-hydroxytryptamine and gamma amino butyric acid, and their relationship to operant behavior, feeding, drinking and locomotion. The actions of neurotransmitters will be modified by drugs and/or neurotoxin. Behavior will be measured using computer-oriented techniques. We will attempt to identify changes in neurotransmitter systems that occur when operant behavior is modified by administration of antidepressant drugs. The goal of this research is to elucidate changes in central nervous system neurochemistry which lead to changes in behavior and which may be involved in the pathophysiology of depression, and attempt to identify neurochemical mechanisms in the central nervous system that account for drug-behavior- environment interactions to further understand the relative roles of drugs and the environment in modifications of behavior. The second aim of the research proposed is to determine whether the long-term alterations in monoamine levels and morphological signs of degeneration -- that we have demonstrated previously in our research on the neurotoxicity produced by administration of amphetamines -- is also produced by other commonly prescribed or abused anorectic and psychomotor stimulant drugs. We will study long-term behavioral changes associated with monoaminergic toxicity produced by methamphetamine and hallucinogenic amphetamine analogues, including MDA and MDMA ((plus/minus)-3,4-methylenedioxymethamphetamine and cocaine. We will continue to examine in detail the mechanism by which methamphetamine and related drugs produce neurotoxic effects. Our results to date have indicated that 6-hydroxydopamine and 5,6-dihydroxytryptamine are formed in brain after a large dose of methylamphetamine. The relationship between the oxidative stress hypothesis and the fact that the blockade of the n-methyl-d-aspartate receptor in protecting against neurotoxicity will also be investigated.

这项拟议研究的长期目标是了解 中枢神经系统神经递质系统在高血压病中的调节作用 精神药物在维持行为方面的作用。 过去几年的实验工作表明，正如 中枢神经系统中的神经递质是由药物改变的， 行为是被修改的，而且，行为和环境都是 对神经递质功能也有影响。因此，一个交互式的 一方面，大脑、神经递质和药物之间存在状态 而环境、行为和神经递质则是另一种。它是 在这个概念框架内，我们将进行具体的研究 未来几年的项目。我们将重点关注多巴胺，去甲肾上腺素， 5-羟色胺和γ-氨基丁酸及其与 活动行为、进食、饮水和运动。的行为 神经递质将被药物和/或神经毒素改变。行为 将使用面向计算机的技术进行测量。我们将尝试 确定神经递质系统在运行时发生的变化 行为可以通过服用抗抑郁药物来改变。目标是 这项研究的目的是阐明中枢神经系统的变化 导致行为改变的神经化学，这可能与 在抑郁症的病理生理学方面，并试图识别神经化学物质 中枢神经系统中解释药物行为的机制- 环境相互作用进一步了解药物的相关作用 以及环境对行为的改变。的第二个目标 提出的研究是为了确定长期的变化是否 单胺水平和退化的形态迹象--我们有 先前在我们对以下物质产生的神经毒性的研究中证明 服用安非他明--也是由其他常见的 处方或滥用厌食药和精神运动兴奋剂。我们会 研究与单胺能毒性相关的长期行为变化 由甲基苯丙胺和致幻安非他明类似物产生， 包括mda和mdma((plus/minus)-3，4-methylenedioxymethamphetamine以及 可卡因。我们会继续详细研究 甲基苯丙胺和相关药物会产生神经毒性作用。我们的结果 迄今已表明6-羟基多巴胺和5，6-二羟色胺 是在大剂量甲基苯丙胺后在大脑中形成的。这个 氧化应激假说与以下事实之间的关系 阻断N-甲基-D-天冬氨酸受体在抗病毒中的作用 神经毒性也将被调查。