Role of MOR1 up-regulation in relapse to cocaine seeking

描述(由申请人提供)： 复吸行为与戒断慢性可卡因自身用药时间的增加有关。以前的研究发现，MOR1的上调与可卡因的使用之间存在关系。利用啮齿动物可卡因自身给药模型，通过阿片受体蛋白印迹和受体下游靶点的激活以及戒断过程中对阿片类药物刺激的行为反应，本研究拟确定慢性可卡因戒断过程中伏核(NAC)中MOR1功能上调的时间框架。此外，这项研究还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会话内恢复范例的动物中调节复发行为的作用。病毒介导的MOR1过表达和下调将被用于研究MOR1在线索、压力和药物诱导的复发中的作用。这项研究可能会阐明治疗或预防神经适应的新策略，这些适应增加了药物成瘾者的复发倾向。

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.