DOPAMINE PARTIAL AGONISTS AND PSYCHOSTIMULANT DEPENDENCE

多巴胺部分激动剂和精神兴奋剂依赖性

• 批准号: 6778324
• 负责人: George F. Koob
• 金额: $ 32.41万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-15 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6778324
• 关键词: behavior test; behavioral /social science research tag; behavioral habituation /sensitization; dopamine agonists; dopamine antagonists; dopamine receptor; drug abuse chemotherapy; drug addiction; drug addiction antagonist; drug interactions; drug withdrawal; electrophysiology; laboratory rat; methamphetamine; nonhuman therapy evaluation; operant conditionings; reinforcer; self medication; substance abuse related behavior

DESCRIPTION: (Adapted from the Investigator's Abstract) This proposal seeks to extend the focus of investigation conducted during the previous funding period, which was concerned with the effects of dopamine D2 partial agonists on multiple measures of cocaine self-administration and withdrawal, to study the neuropharmacology of methamphetamine dependence. Work during the previous funding period has allowed the characterization of the effects of dopamine D2 partial agonists on both cocaine and amphetamine self-administration under conditions of limited daily access and across full dose effect functions. In addition, the addictive liability of partial agonists has been examined showing that terguride, a prototype dopamine D2 partial agonist, does not function as a substrate for self-administration and does not act as a priming agent reinstating extinguished self-administration. Furthermore, initial studies have addressed the hypothesis that partial dopamine agonists may also act as candidates for pharmacotherapy for amphetamine and methamphetamine dependence. The aim of the proposed studies is to further characterize the effects of partial dopamine agonists acting on D1, D2 and D3 dopamine receptor subtypes on methamphetamine dependence. For this purpose, a variety of animal tests tailored to model several components of the methamphetamine dependence cycle will be employed. The guiding hypothesis of the present proposal is that dopamine partial agonists may provide innovative pharmacological measures of interaction with multiple aspects of methamphetamine-seeking behavior that may ultimately lead to the loss of control which represents the cardinal feature of the psychostimulant addictive cycle. A detailed characterization of the effects of dopamine partial agonists on multiple measures of methamphetamine self-administration will allow insight into the effects of these drugs on the acute reinforcing properties of methamphetamine in Specific Aim 1. Specific Aim 2 and 3 will examine the abstinence phase investigating the potential of partial agonists to prevent different behavioral changes associated with withdrawal. The potential of partial agonists to induce relapse or prevent methamphetamine-induced relapse of methamphetamine-seeking behavior will also be evaluated. Specific Aim 4 will then characterize the transition from moderate to excessive methamphetamine-seeking behavior and investigate whether partial dopamine agonists modify drug intake in rats with a history of drug escalation.

描述：（改编自研究者摘要）本提案旨在 扩大上一个供资期间进行的调查重点， 这是关于多巴胺D2部分激动剂对 可卡因自我给药和戒断的多种措施，以研究 甲基苯丙胺依赖的神经药理学工作在前 资助期间允许多巴胺D2的影响的表征 可卡因和安非他明自我给药的部分激动剂 有限的每日访问和全剂量效应函数的条件。在 此外，部分激动剂的成瘾倾向已被检查，显示 一种原型多巴胺D2部分激动剂， 用于自我给药的基质，不作为引发剂 恢复被消灭的自治。此外，初步研究 提出了部分多巴胺激动剂也可能作为 安非他明和甲基安非他明依赖药物治疗的候选人。 拟议研究的目的是进一步表征 作用于D1、D2和D3多巴胺受体亚型的部分多巴胺激动剂， 对冰毒的依赖为此，进行了各种动物试验。 专门用于模拟甲基苯丙胺依赖循环的几个组成部分 将被雇用。本提案的指导假设是， 多巴胺部分激动剂可以提供创新的药理学措施， 与寻求甲基苯丙胺行为的多个方面的相互作用， 最终导致失去控制，这代表了 精神兴奋剂成瘾循环对影响的详细描述 多巴胺部分激动剂对多种甲基苯丙胺的影响 自我管理将允许深入了解这些药物的影响， 《特殊目标1》中甲基苯丙胺的急性强化特性。具体目标 2和3将检查禁欲阶段，调查 部分激动剂，以防止不同的行为变化相关的 戒断部分激动剂诱导复发或预防 甲基苯丙胺诱导的甲基苯丙胺寻求行为的复发也会 被评价。具体目标4将描述从 中度到过量的甲基苯丙胺寻求行为，并调查是否 部分多巴胺激动剂改变有药物史大鼠的药物摄入 升级