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: 7315385
• 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/7315385
• 关键词: Abstinence; Addictive Behavior; Agonist; Animals; Anterior; Behavior; Behavioral; Chronic; Cocaine; Cues; Down-Regulation; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Gene Expression; Individual; Infusion procedures; Injection of therapeutic agent; Mediating; Modeling; Morus; Neurobiology; Nucleus Accumbens; Opioid; Opioid Receptor; Pharmaceutical Preparations; Phosphorylation; Prevention; Procedures; Protein Overexpression; Purpose; RNA Interference; Rate; Rattus; Receptor Activation; Relapse; Rodent; Role; Self Administration; Stress; Testing; Time; Time Study; Transcriptional Activation; Up-Regulation; Viral; Week; Western Blotting; Withdrawal; drug addict; drug of abuse; in vivo; knock-down; mu opioid receptors; neuroadaptation; receptor; response; tool

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）： 复发行为与慢性可卡因自我给药戒断期增加相关。先前的研究发现MOR1的上调与可卡因给药之间存在关系。使用啮齿动物中的可卡因自我给药模型，拟议的研究计划使用阿片受体的Western印迹和受体下游靶点的激活以及戒断期间对阿片刺激的行为反应来确定慢性可卡因自我给药戒断期间中脑核（NAc）中功能性MOR1上调的时间范围。此外，本研究将进一步研究MOR1在NAc核心和外壳中的作用，在使用阿片受体激动剂和拮抗剂进行会话内恢复范例的动物中调节复发行为。病毒介导的MOR1过表达和敲低将用于研究MOR1对线索、应激和药物诱导的复发的影响。这项研究可能阐明新的策略，治疗或预防神经适应，增加复发的倾向，在吸毒成瘾的个人。