Role of MOR1 up-regulation in relapse to cocaine seeking

MOR1上调在可卡因寻求复发中的作用

• 批准号: 7057722
• 负责人: DIANA L SIMMONS
• 金额: $ 3.15万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7057722
• 关键词: cocaine; role

DESCRIPTION (provided by applicant): Relapse behaviors associated with increasing periods of withdrawal from chronic cocaine self-administration. Previous studies find a relationship between the upregulation of MOR1 and cocaine administration. Using the cocaine self-administration model in rodents, the proposed study plans to determine the time-frame of functional MOR1 upregulation in nucleus accumbens (NAc) during withdrawal from chronic cocaine selfadministration using Western blot of opioid receptors and activation of receptor downstream targets and behavioral responses to opioid stimulation during withdrawal. In addition, this study will pharmacologically investigate the role of MOR1 in NAc core and shell in modulating relapse behavior in animals undergoing a within-session reinstatement paradigm using opioid receptor agonists and antagonists. Viral- mediated MOR1 overexpression and knock-down will be used to study MOR1 effects on cue-, stress-, and drug-induced relapse. This study may elucidate new strategies for the treatment or the prevention of neuroadaptations that increase the propensity for relapse in drug addicted individuals.

描述（由申请人提供）： 与长期可卡因自我给药戒断期延长相关的复发行为。先前的研究发现 MOR1 的上调与可卡因服用之间存在关系。利用啮齿动物的可卡因自我给药模型，拟议的研究计划利用阿片受体的蛋白质印迹、受体下游靶标的激活以及戒断期间对阿片类刺激的行为反应，确定长期可卡因自我给药戒断期间伏隔核（NAc）功能性MOR1上调的时间范围。此外，本研究将从药理学角度研究 NAc 核心和外壳中的 MOR1 在使用阿片受体激动剂和拮抗剂进行疗程内恢复范例的动物中调节复发行为中的作用。病毒介导的 MOR1 过表达和敲低将用于研究 MOR1 对线索、压力和药物诱导的复发的影响。这项研究可能会阐明治疗或预防神经适应的新策略，这些神经适应会增加吸毒者复发的可能性。