BRAIN MONOAMINES, DRUGS AND CONDITIONED BEHAVIOR

拟议研究的第一个长期目标是 了解中枢神经系统神经递质 系统发挥作用的精神药物的影响， 行为的维持。 我们将重点关注多巴胺（DA）， 去甲肾上腺素（NE）和5-羟色胺（5 HT），以及它们的 与操作行为的关系。 进食、饮水和 运动也将被研究，因为它们是重要的 操作行为的组成部分。 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。 我们将测量神经递质系统的变化， 当操作性行为被修改的管理发生 抗抑郁药 这项研究的目的是阐明 中枢神经系统神经化学的变化， 行为的变化，以及可能涉及的 抑郁症的病理生理学 我们将测量 作为行为的函数， 对于药物-行为-环境相互作用， 了解药物和环境的相对作用， 行为的修改。 研究的第二个目的是确定 单胺水平的长期变化， 先前在 我们对甲基苯丙胺神经毒性的研究， 由其他处方或滥用的厌食剂产生， 精神兴奋剂 苄非他明，苯甲曲嗪， 苯甲曲嗪、芬特明、氯特明和可卡因将被 检查神经毒性。 我们将研究长期的行为 与单胺能毒性相关的变化 甲基安非他明和致幻安非他明类似物， 包括3，4-亚甲二氧基苯丙胺（MDA）和3，4- 亚甲二氧基甲基苯丙胺（MDMA）和可卡因。 第三个目的是详细审查 甲基苯丙胺和相关药物产生神经毒性作用。 我们的研究结果表明，6-羟基多巴胺（6- OHDA）和5，6-二羟色胺（5，6-DHT）在 大量冰毒后的大脑 我们建议 证实6-OHDA和5，6-DHT在大脑中形成， DA或5 HT，使用气相色谱和质谱法。 我们还将研究这种反应的条件 发生在体外、离体和体内。

The first long-range aim of the proposed research is to understand the role central nervous system neurotransmitter systems play in the action of psychotropic drug effects and in the maintenance of behavior. We will focus on dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5HT), and their relationship to operant behavior. Feeding, drinking and locomotion will also be studied since they are important components of operant behavior. The actions of neurotransmitters will be modified by drugs and/or neurotoxins. Behavior will be measured using computer-oriented techniques. We will measure changes in neuro-transmitter 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. We will measure the changes in transmitter turnover as a function of behavior that may 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 proposed research is to determine whether the long-term alternations in monoamine levels and morphological signs of degeneration demonstrated previously in our research on the neurotoxicity of methamphetamine, is also produced by other prescribed or abused anorectics and psychomotor stimulants. Benzphetamine, phenmetrazine, phendimetrazine, phentermine, chlortermine and cocaine will be examined for neurotoxicity. We will study long-term behavioral changes associated with monoaminergic toxicity produced by methamphetamine and hallucinogenic amphetamine analogs, including 3,4-methylenedioxyamphetamine (MDA) and 3,4- methylenedioxymethamphetamine (MDMA), and cocaine. The third aim is to examine in detail the mechanism by which methamphetamine and related drugs produce neurotoxic effects. Our results to date have indicated that 6-hydroxydopamine (6- OHDA) and 5,6-dihydroxytryptamine (5,6-DHT) are formed in brain after a large dose of methamphetamine. We propose to confirm that 6-OHDA and 5,6-DHT are formed in the brain from DA or 5HT using gas chromatography and mass spectrometry. We shall also study the conditions under which this reaction occurs in vitro, ex vivo, and in vivo.