BEHAVIORAL PHARMACOLOGY OF ACUTE AND CHRONIC AMPHETAMINE

NIDA最近的一项调查显示，兴奋剂显著增加 虐待。这一证据强调了在 动物的行为特征及其相应的神经化学系统(S) 以及与不同兴奋剂滥用模式相关的机制(S)。 拟议研究的主要目标是扩展以前的工作 不同剂量不同药物对小鼠行为和神经化学影响的研究 大鼠暴露于苯丙胺类兴奋剂的剂量和持续时间。 单次和多次重复行为效应的评估 将延长低至中等剂量兴奋剂的给药时间 我们增强的自动化和观察性监控系统可提供更多 准确和彻底地描述刺激性反应。在……里面 除了运动和集中的类固醇，行为测量现在是 可以用来评估我们的假设，反应的坚持性和 与环境的接触代表着重要的行为维度 刺激性反应。去甲肾上腺素、多巴胺和5-羟色胺系统在 提出了这些行为维度，并设计了研究来验证 这些假设。此外，一种提出的神经化学机制 刺激剂诱导的运动的剂量相关转变的基础 对聚焦刻板印象的激活也将进行评估。我们以前的 研究表明，不同模式和剂量的重复刺激剂 给药会使兴奋剂的各种成分发生变化 以行为增强、耐受性和/或 缩短了响应持续时间。这些现象将被进一步研究。 通过检查年龄和压力相关的差异对重复的反应 并通过评估可能参与的兴奋剂治疗 发育中的内源性阿片和单胺系统及其机制 这些影响。此外，我们还将考察“突发事件”行为 由大剂量、急性兴奋剂或持续服用所产生的综合征 中毒方案和与中枢神经系统毒性相关，特别是 关于确定这些证候与证型的关系 在人类身上滥用兴奋剂。拟议的研究将利用各种 行为学、药理学、神经化学和电生理学 描述行为和潜在机制的技术 与不同的兴奋剂给药模式有关。这些 研究可能会提供有关持续性影响的重要信息 由于长期服用兴奋剂，两者之间的相互作用 兴奋剂和其他滥用药物，以及针对特定药物的可能治疗方法 对人体有不良影响。

A recent survey by NIDA indicates a significant increase in stimulant abuse. This evidence underscores the importance of characterizing in animals the behavioral profiles and corresponding neurochemical system(s) and mechanism(s) associated with different patterns of stimulant abuse. The primary objective of the proposed research is to extend previous work on the various behavioral and neurochemical effects induced by different doses and durations of exposure to amphetamine-like stimulants in rats. Assessments of the behavioral effects induced by single and repeated administration of low to moderate stimulant doses will be extended using our enhanced automated and observational monitoring systems to provide more accurate and thorough characterizations of the stimulant response. In addition to locomotion and focused sterotypies, behavioral measures are now available to evaluate our hypothesis that response perseveration and engagement with the environment represent important behavioral dimensions of the stimulant response. Specific roles for NE, DA, and 5-HT systems in these behavioral dimensions are proposed and studies are designed to test these hypotheses. In addition, a proposed neurochemical mechanism underlying the dose-related transition from stimulant-induced locomotor activation to focused stereotypies will also be assessed. Our previous studies revealed that different patterns and doses of repeated stimulant administration produce alterations in various components of the stimulant response in the form of behavioral augmentation, tolerance, and/or shortened response duration. These phenomena will be further investigated by examining age- and strain-related differences in response to repeated stimulant administration and by assessing the possible involvement of endogenous opioid and monoamine systems and mechanisms in the development of these effects. In addition, we will also examine "emergent" behavioral syndromes produced by high, acute stimulant doses or continuous intoxication regimens and associated with CNS neurotoxicity, particularly with respect to determining the relationship of these syndromes to patterns of stimulant abuse in humans. The proposed research will utilize a variety of behavioral, pharmacological, neurochemical, and electrophysiological techniques to characterize the behaviors and underlying mechanisms associated with different patterns of stimulant administration. These studies may provide important information regarding persistent effects resulting from chronic stimulant administration, interactions between stimulants and other drugs of abuse, and potential treatments for specific adverse effects in humans.