Opioid and Dopamine Mechanisms of Heroin Relapse

阿片类药物和多巴胺导致海洛因复吸的机制

• 批准号: 7072710
• 负责人: Glenn R Valdez
• 金额: $ 0.34万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7072710
• 关键词: Macaca mulatta; behavioral /social science research tag; cocaine; craving; dopamine agonists; dopamine antagonists; dopamine receptor; drug abuse; heroin; inhibitor /antagonist; neuropharmacology; opioid receptor; postdoctoral investigator; relapse /recurrence; stimulant /agonist; substance abuse related behavior

DESCRIPTION (provided by applicant): The objective of the proposed studies is to develop a nonhuman primate model of heroin relapse to investigate the specific neuropharmacological mechanisms underlying the reinstatement of heroin-seeking behavior. High rates of relapse following periods of extended abstinence are typically experienced by many heroin users, further contributing to the challenge of long-term management of heroin addiction. The specific biological mechanisms, however, underlying this continued heroin-seeking behavior remain incompletely understood. Specific Aim 1 will further our knowledge of the regulation of heroin relapse via opioid receptor mechanisms by examining the effects of antagonists and agonists selective in binding to the mu and delta opioid receptors on heroin priming-induced reinstatement of heroin seeking. Specific Aim 2 will use a conceptually similar strategy to investigate the function of D1-like and D2-like dopamine receptor mechanisms in heroin reinstatement. Specific Aim 3 will seek to determine the ability of cocaine to reinstate heroin-seeking behavior, and the associated neurochemical mechanisms, in order to determine if priming-induced reinstatement generalizes to drugs that are often co-abused with heroin.

描述（由申请人提供）：拟议研究的目的是开发海洛因复发的非人类灵长类动物模型，以研究海洛因寻求行为恢复的具体神经药理学机制。许多海洛因吸食者通常会经历长期戒毒后的高复发率，这进一步加剧了海洛因成瘾长期管理的挑战。然而，这种持续的海洛因寻求行为背后的具体生物学机制仍不完全清楚。具体目标 1 将通过检查选择性结合 mu 和 delta 阿片受体的拮抗剂和激动剂对海洛因启动诱导的海洛因寻求恢复的影响，进一步加深我们对通过阿片受体机制调节海洛因复发的认识。具体目标 2 将使用概念上类似的策略来研究 D1 样和 D2 样多巴胺受体机制在海洛因恢复中的功能。具体目标 3 将寻求确定可卡因恢复海洛因寻求行为的能力以及相关的神经化学机制，以确定启动诱导的恢复是否适用于经常与海洛因共同滥用的药物。