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.

拟议研究的远程目标是了解角色 中枢神经系统神经递质系统在调解中播放 精神药物的作用和维持行为。 过去几年的实验工作表明， 中枢神经系统中的神经递质通过药物修饰， 行为被修改，进一步的行为和环境 还对神经递质功能产生影响。 因此，互动 一方面存在状态在大脑，神经递质和药物之间 另一个环境，行为和神经递质。 这是 在这个概念框架内，我们将进行特定的研究 未来几年的项目。 我们将专注于多巴胺，去甲肾上腺素， 5-羟色胺和伽马氨基丁酸，它们与 操作行为，喂养，饮酒和运动。 行动 神经递质将通过药物和/或神经毒素修饰。 行为 将使用面向计算机的技术进行测量。 我们将尝试 确定操作员时发生的神经递质系统的变化 行为是通过抗抑郁药的给药来改变的。 目标 这项研究是为了阐明中枢神经系统的变化 神经化学导致行为变化并可能涉及 在抑郁症的病理生理学中，并试图鉴定神经化学 中枢神经系统中的机制解释了药物行为 - 环境相互作用以进一步了解药物的相对作用 以及行为修改的环境。 第二个目标 提出的研究是确定是否长期改变 单胺水平和变性的形态迹象 - 我们有 先前在我们关于由神经毒性的研究中证明了 苯丙胺的给药 - 也是其他常见的 处方或滥用厌食和精神运动刺激药物。 我们将 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苯丙胺类似物产生， 包括MDA和MDMA（（（加/减）-3,4-甲基二甲基甲基苯丙胺和 可卡因。 我们将继续详细研究 甲基苯丙胺和相关药物产生神经毒性作用。 我们的结果 迄今为止已经表明6-羟基多巴胺和5,6-二羟基丙胺胺 大剂量的甲基苯丙胺在大脑中形成。 这 氧化应激假说与事实之间的关系 封闭N-甲基-D-天冬氨酸受体的封锁 神经毒性也将被研究。