NEUROCHEMISTRY UNDERLYING STIMULANT INDUCED BEHAVIORS

安非他明、可卡因和类似的兴奋剂会引起剂量相关的 从广泛性唤醒到刻板印象的转变及其机制 这一转变的背后可能会对药物滥用产生重要影响。 我们先前和正在进行的在清醒状态下使用活体微透析的研究 动物们继续证明，这种转变与 大小和时间上的区域性多巴胺反应 特征，并且我们假设过渡涉及 多巴胺与其他递质的相互作用，包括5-羟色胺和 去甲肾上腺素。就多巴胺反应的大小而言， 当多巴胺释放剂(例如， 苯丙胺)和多巴胺摄取阻滞剂(例如可卡因)进行比较， 也让我们假设发射机的大小 对释放物兴奋剂的反应可能并不总是反映行为 相关的突触多巴胺。为了检验这一假设，我们将检验 功能性多巴胺传递的替代方法。此外， 不同的药物特异性调控过程对行为 这些药物的简介。因此，amph增加了细胞外多巴胺。 (并且，我们假设，。去甲肾上腺素和5-羟色胺)主要通过 释放过程不依赖于神经元的脉冲流。通过 相比之下，神经递质对可卡因等摄取阻滞剂的反应， 是由自身感受器功能和脉冲流的水平决定的 假设在个体差异中起着重要作用 行为反应性与神经化学的区域差异 对可卡因类兴奋剂的反应。为了检验我们的假设，我们将 扩大我们对摄取阻滞剂和 行为和局部多巴胺、去甲肾上腺素和5-羟色胺的释放剂。 此外，还将使用各种药理操作来 研究神经元冲动流、自身受体功能、 以及细胞质和囊泡递质池的动力学 兴奋剂诱导的行为和细胞外递质的变化。这 伴随着对突触递质动力学的更广泛的评估 行为分析应该进一步阐明各种因素的作用 神经递质系统和机制在从兴奋剂- 诱导运动到行为的持久化。

Amphetamine, cocaine, and similar stimulants induce a dose-related transition from generalized arousal to stereotypies, and the mechanisms underlying this transition may have important implications for drug abuse. Our previous and ongoing research using in vivo microdialysis in awake animals continues to demonstrate that this transition is dissociated from the regional dopamine response with regard to magnitude and temporal characteristics, and we have hypothesized that the transition involves the interaction of dopamine with other transmitters, including serotonin and norepinephrine. In terms of the magnitude of the dopamine response, the dissociation is particularly evident when dopamine releasers (e.g., amphetamine) and dopamine uptake blockers (e.g., cocaine) are compared, and has also lead us to hypothesize that the magnitude of the transmitter response to releaser stimulants may not always reflect behaviorally relevant synaptic dopamine. To test this hypothesis, we will examine alternative measures of functional dopamine transmission. Furthermore, different drug-specific regulatory processes contribute to the behavioral profiles of these drugs. Thus, AMPH increases extracellular dopamine (and, we hypothesize,. norepinephrine and serotonin) primarily through a release process which is independent of neuronal impulse flow. By contrast, the neurotransmitter response to uptake blockers like cocaine, is dictated by levels of autoreceptor function and impulse flow which we hypothesize play a significant role in the individual variations in behavioral responsiveness and in the regional differences in neurochemical response to cocaine-like stimulants. To test our hypotheses, we will extend our characterization of the effects of uptake blockers and releasers on behavior and regional dopamine, norepinephrine and serotonin. In addition, a variety of pharmacological manipulations will be used to examine the contribution of neuronal impulse flow, autoreceptor function, and the dynamics of cytoplasmic and vesicular transmitter pools to stimulant-induced behavior and changes in extracellular transmitter. This more extended evaluation of synaptic transmitter dynamics concomitant with behavioral analysis should further elucidate the role of various neurotransmitter systems and mechanisms in the transition from stimulant- induced locomotion to behavioral perseveration.