NEUROCHEMISTRY UNDERLYING STIMULANT INDUCED BEHAVIORS

安非他明、可卡因和类似兴奋剂诱导剂量相关的 从一般性唤起到刻板印象的转变， 这一转变可能对药物滥用产生重要影响。 我们以前和正在进行的研究使用体内微透析在清醒 动物继续证明，这种转变是分离的， 局部多巴胺反应的幅度和时间 特征，我们假设过渡涉及 多巴胺与其他递质的相互作用，包括血清素和 去甲肾上腺素 就多巴胺反应的幅度而言， 当多巴胺释放剂（例如， 安非他明）和多巴胺摄取阻断剂（例如，可卡因）进行比较， 这也让我们假设发射器的大小 对激光兴奋剂的反应可能并不总是反映行为 相关的突触多巴胺 为了验证这一假设，我们将研究 功能性多巴胺传递的替代措施。 此外，委员会认为， 不同的药物特异性调节过程有助于行为 这些药物的特征。 因此，AMPH增加细胞外多巴胺 (and，我们假设，。去甲肾上腺素和血清素）主要通过 这是独立于神经冲动流的释放过程。 通过 相反，神经递质对可卡因等吸收阻滞剂的反应， 由自身感受器功能和冲动流的水平决定， 假设在个体差异中起重要作用， 行为反应性和神经化学的区域差异 对可卡因样兴奋剂的反应 为了验证我们的假设，我们将 扩展我们对摄取阻滞剂作用的表征， 释放行为和局部多巴胺、去甲肾上腺素和血清素。 此外，将使用各种药理学操作， 检查神经冲动流，自身感受器功能， 以及细胞质和囊泡递质池的动力学， 刺激剂诱导的行为和细胞外递质的变化。这 更广泛的评估突触递质动力学伴随着 行为分析应进一步阐明各种 神经递质系统和机制的过渡，从兴奋剂- 诱导运动到行为持续。

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.