BEHAVIORAL PHARMACOLOGY OF ACUTE AND CHRONIC AMPHETAMINE

彻底的行为表征的急性和慢性 实验动物中的安非他明特征是必要的 阐明心理学和神经生物学的先决条件 涉及安非他明滥用倾向的过程以及 受到人类各种使用模式的影响。 几 实验方法可能有助于确定 与临床相关的特定行为。 除了有 使用模拟各种滥用模式的给药方案， 比较产生影响的精神兴奋剂， 类似于安非他明的人类（例如，可卡因）与那些做 不（例如，咖啡因）也可以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- 具体的回答。 两个这样的维度， 几乎所有服用安非他明类兴奋剂的动物都是 反应的持续性质量和相应的 减少与环境的相互作用。 一些证据表明 中纹状体多巴胺和血清素系统可能在 而环境参与的程度 可能是由背部活动的平衡来调节的。 去甲肾上腺素能系统和中脑边缘肾上腺素能系统。 选择性单胺损害的研究旨在测试 这些假设。 有证据表明， 行为反应的特定成分的出现， 刺激物与实验条件密切相关， 表现出严格的时间模式， 动物 然而，大多数生物化学研究都使用 但不一定与行为相关 实验条件和时间点，并已忽略 反应的个体差异。 更多相关生化 数据将在个体动物的研究中获得， 已经评估了行为特征。 另外由于 与死后生化检查相关的局限性 分析，研究也计划使用推拉灌注 技术来测量突触递质水平在自由 移动的动物 这种方法提供了一种连续的测量方法， 整个行为时间过程中的神经递质动力学， 并允许每只动物作为自己的对照。 我们正在进行的 拟议的研究代表了一种多学科的方法， 在表征由以下物质产生的刺激效应的光谱方面， 与各种模式相关的剂量方案的范围 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.