BEHAVIORAL PHARMACOLOGY OF ACUTE AND CHRONIC AMPHETAMINE

急性和慢性患者的彻底行为特征 实验动物的苯丙胺图谱是必要的 阐明心理和神经生物学的前提条件 涉及苯丙胺滥用责任的过程以及 受人类各种使用模式的影响。几个 实验方法可能有助于识别 临床上相关的特定行为。除 使用模拟各种滥用模式的给药方案， 精神运动刺激剂对人体健康影响的比较 与安非他明(如可卡因)相似的人 非咖啡因(例如，咖啡因)也可能提供有用的行为和神经- 化学信息。另一种方法涉及 识别超越物种的行为维度- 具体的回应。两个这样的维度在 几乎所有给予安非他明类兴奋剂的动物都是 坚持不懈的反应质量和相应的 环境相互作用减少。一些证据表明 中纹状体多巴胺和5-羟色胺系统可能起到一定的作用 坚持不懈，而环境参与的程度 可能受背部活动的平衡所调节 去甲肾上腺素能系统和中脑边缘5-羟色胺能系统。 对选择性单胺损伤的研究旨在测试 这些假设。越来越多的证据表明 行为反应的特定成分的外观 兴奋剂与实验条件密切相关， 表现出严格的时间模式，并且在 动物。然而，大多数生化研究都使用了 药理上的，但不一定是行为上的 实验条件和时间点，并已忽略 反应的个体差异。更相关的生化 数据将在对单个动物的研究中获得，这些动物 已经对行为特征进行了评估。此外，由于 与死后生化有关的局限性 分析、研究也计划使用推拉灌流 自由测量突触递质水平的技术 移动的动物。这种方法提供了一种连续的测量方法 神经递质在整个行为过程中的动态变化， 并允许每种动物充当自己的控制者。我们正在进行的 拟议的研究代表了一种多学科方法，旨在 在描述由以下物质产生的刺激效应的光谱时 与不同模式相关的给药方案的范围 兴奋剂滥用。

Thorough behavioral characterization of the acute and chronic amphetamine profiles in experimental animals is a necessary prerequisite for elucidating the psychological and neurobiological processes implicated in amphetamine abuse liability and those affected by various patterns of usage in humans. Several experimental approaches may facilitate the identification of specific behaviors that are clinically relevant. In addition to the use of dosage regimens which simulate various abuse patterns, comparisons of psychomotor stimulants that produce effects in humans similar to amphetamine (e.g., cocaine) with those that do not (e.g., caffeine) may also provide useful behavioral and neuro- chemical information. Another approach involves the identification of behavioral dimensions that transcend species- specific responses. Two such dimensions that are apparent in virtually all animals given amphetamine-like stimulants are the perseverative quality of the response and the corresponding decreases in environmental interaction. Some evidence suggests that mesostriatal dopamine and serotonin systems may play a role in perseveration whereas the degree of environmental engagement may be regulated by a balance in the activities of the dorsal noradrenergic system and the mesolimbic serotonergic system. Studies with selective monoamine lesions are designed to test these hypotheses. Converging evidence indicates that the appearance of specific components of the behavioral response to stimulants are intimately related to the experimental conditions, exhibit strict temporal patterns, and vary dramatically between animals. However, most biochemical studies have used pharmacologically, but not necessarily behaviorally relevant experimental conditions and time points, and have ignored individual differences in response. More relevant biochemical data would be obtained in studies of individual animals whose behavioral profiles have been assessed. In addition, because of the limitations associated with post-mortem biochemical analyses, studies are also planned using push-pull perfusion techniques to measure synaptic transmitter levels in freely moving animals. This approach provides a continuous measure of neurotransmitter dynamics throughout the behavioral time course, and allows each animals to serve as its own control. Our ongoing and proposed studies represent a multidisciplinary approach aimed at characterizing the spectrum of stimulant effects produced by the range of dosage regimens associated with various patterns of stimulant abuse.