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: 6885124
• 负责人: Glenn R Valdez
• 金额: $ 4.3万
• 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 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885124
• 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）：拟议的研究的目的是开发一种非人类灵长类动物的海洛因复发模型，以研究恢复海洛因寻求行为的特定神经药理机制。许多海洛因使用者通常会经历较高的延长节制后复发率，这进一步促进了海洛因成瘾的长期管理的挑战。然而，具体的生物学机制是基于这种持续的寻求海洛因寻求行为的行为尚未完全理解。特定的目标1将通过研究拮抗剂和激动剂在与MU和Delta阿片类药物对海洛因引发引起的海洛因寻求海洛因恢复时的结合方面的影响，进一步我们通过阿片类受体机制来调节海洛因复发的了解。特定的目标2将使用概念上类似的策略来研究恢复海洛因中D1样和D2样多巴胺受体机制的功能。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，以确定启动引发诱导的恢复是否会推广到通常与海洛因共同置换的药物。