BEHAVIORAL MEASURES OF TOLERANCE AND WITHDRAWAL

容忍和戒断的行为措施

• 批准号: 3214752
• 负责人: WILLIAM F CAUL
• 金额: $ 11.14万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3214752
• 关键词: amphetamines; behavior test; behavioral habituation /sensitization; biological models; cocaine; discrimination learning; drug tolerance; drug withdrawal; haloperidol; laboratory rat

Drug-discrimination procedures with animals have been used to model drug-induced changes in mood in humans. Our previous research, using a two-choice discrimination, has shown that time-dependent, bidirectional changes in choice responding occur following administration of drug. We have also shown that knowledge of the time course of this bidirectional shift is important for understanding the effects of repeated drug administration as well as agonist-antagonist interactions. These findings suggest that the phenomena of pharmacodynamic tolerance, withdrawal, and drug-dependence can be understood in terms of normal, adaptive processes. Research is needed, however, to establish the degree of specificity of the rebound or adaptive state that follows the primary drug effect. Because both the drug-induced primary cue state and any subsequent rebound state must be defined relative to the "normal" state, unambiguous definition of "normal" is required. The proposed research will do this by using a three-choice drug- discrimination task that includes a specific saline-appropriate response alternative. The initial experiment will characterize the time- dependent changes in cue state following single doses of amphetamine and cocaine. Then, the extent to which these bidirectional changes mediate drug withdrawal and drug tolerance will be determined. The results of these studies will define parameters that will then be used to assess the extent to which interdose intervals can be chosen to either optimize or preclude tolerance resulting from repeated drug administration. The final experiment will determine if the post-amphetamine withdrawal state is an effective cue for discrimination learning. If learning occurs as expected, the withdrawal state will be further characterized by identifying drugs with cue properties that will substitute for it. The unique aspects of this research are its ability to measure adaptive processes that oppose the primary effect of psychoactive drugs, and its emphasis on characterizing the effects of drugs in terms of bidirectional changes over time. The results of the studies proposed should (1) contribute to an understanding of adaptive processes underlying tolerance, withdrawal, and sensitization, and (2) help establish the relevance of the drug-discrimination model to questions of drug use by humans.

用动物的药物歧视程序已用于建模 药物引起的人类情绪变化。 我们以前的研究，使用 两项选择的歧视表明，时间依赖于双向 服用药物后，选择反应的变化发生。 我们 还表明了该双向时间过程的知识 转移对于理解重复药物的影响很重要 给药以及激动剂 - 抗逆邦互动。 这些 调查结果表明，药效耐受的现象， 戒断和药物依赖性可以从正常情况下理解 自适应过程。 但是，需要研究以建立 反弹或适应状态的特异性程度 主要药物作用。 因为药物诱导的原发性提示状态 并且随后的任何反弹状态都必须相对于 “正常”状态，需要“正常”的明确定义。 这 拟议的研究将通过使用三个选择药物来做到这一点 歧视任务，包括特定盐水的反应 选择。 最初的实验将表征时间 - 单剂量的苯丙胺和 可卡因。 然后，这些双向变化的介导程度 将确定药物提取和药物耐受性。 结果 这些研究将定义参数，然后将其用于评估 可以选择分子间隔以优化的程度 或排除反复给药产生的公差。 这 最终实验将确定苯丙胺后戒断状态是否 是歧视学习的有效提示。 如果学习是 预计，撤回状态将进一步以 识别具有提示特性的药物可以代替它。 这 这项研究的独特方面是它衡量自适应的能力 反对精神药物的主要作用的过程及其 强调以 双向随着时间的变化。 提出的研究结果 应该（1）有助于理解自适应过程 潜在的耐受性，提取和敏化，（2）帮助 建立毒品歧视模型与问题的相关性 人类吸毒。