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.

拟议研究的长期目标是了解 中枢神经系统神经递质系统在介导 精神药物的作用和行为的维持。 过去几年的实验工作表明， 中枢神经系统中的神经递质被药物改变， 行为被修改，而且，行为和环境 也会影响神经递质的功能 因此，一个互动 一方面，大脑、神经递质和药物之间存在着一种状态 另一方面是环境、行为和神经递质。 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。 我们会关注多巴胺，去甲肾上腺素， 5-羟色胺和γ-氨基丁酸，以及它们与 操作性行为进食饮水和运动 的行动 神经递质将被药物和/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 识别神经递质系统的变化， 通过服用抗抑郁药物来改变行为。 目标 这项研究的目的是阐明中枢神经系统的变化， 导致行为变化且可能涉及的神经化学 在抑郁症的病理生理学，并试图确定神经化学 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 和环境对行为的影响 第二个目标 这项研究的目的是确定是否长期的变化， 单胺水平和退化的形态学迹象， 在我们之前对神经毒性的研究中， 安非他明的管理-也是由其他常见的 处方或滥用厌食和精神兴奋剂药物。 我们将 研究与单胺能毒性相关的长期行为变化 由甲基安非他明和致幻安非他明类似物产生， 包括MDA和MDMA（（加/减）-3，4-亚甲二氧基甲基苯丙胺和 可卡因 我们会继续详细研究 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5，6-二羟色胺 是在大剂量甲基苯丙胺后在大脑中形成的 的 氧化应激假说和事实之间的关系， 阻断N-甲基-D-天冬氨酸受体， 还将研究神经毒性。