BEHAVIORAL PHARMACOLOGY OF ACUTE AND CHRONIC AMPHETAMINE

急性和慢性苯丙胺的行为药理学

• 批准号: 3206955
• 负责人: DAVID S SEGAL
• 金额: $ 16.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-06-29 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3206955
• 关键词: amphetamines; behavior disorders; behavior test; catecholamines; central nervous system stimulants; chordate locomotion; dosage; drug adverse effect; electrophysiology; high performance liquid chromatography; neurochemistry; neurotoxins; phencyclidine; psychobiology; psychological stressor; psychomotor disorders; psychopharmacology; psychosis

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.

NIDA 最近的一项调查显示兴奋剂显着增加 虐待。 这一证据强调了表征的重要性 动物的行为特征和相应的神经化学系统 以及与不同类型的兴奋剂滥用相关的机制。 拟议研究的主要目标是扩展以前的工作 不同行为和神经化学效应的影响 大鼠接触苯丙胺类兴奋剂的剂量和持续时间。 评估单次和重复引起的行为影响 低至中度兴奋剂的施用将延长使用 我们增强的自动化和观察监测系统可提供更多 刺激反应的准确和彻底的表征。 在 除了运动和集中刻板印象之外，行为测量现在也 可用于评估我们的假设，即反应坚持和 与环境的接触代表了重要的行为维度 的刺激反应。 NE、DA 和 5-HT 系统在 提出了这些行为维度，并设计了研究来测试 这些假设。 此外，提出的神经化学机制 兴奋剂诱导运动的剂量相关转变的基础 还将评估对集中定型观念的激活情况。 我们之前的 研究表明，不同模式和剂量的重复兴奋剂 给药会导致兴奋剂的各种成分发生变化 以行为增强、耐受性和/或 缩短响应时间。 这些现象将进一步调查 通过检查与年龄和应变相关的差异来应对重复的 兴奋剂管理并通过评估可能的参与 内源性阿片类药物和单胺系统和机制的发展 这些影响。 此外，我们还将检查“紧急”行为 高、急性兴奋剂剂量或连续服用所产生的综合征 中毒方案并与中枢神经系统神经毒性相关，特别是 关于确定这些综合症与模式的关系 人类滥用兴奋剂。 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 表征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 研究可能提供有关持续影响的重要信息 由于长期服用兴奋剂，之间的相互作用 兴奋剂和其他滥用药物，以及针对特定情况的潜在治疗方法 对人体产生不良影响。