KAPPA OPIOIDS INDUCE REINSTATEMENT OF COCAINE-SEEKING VIA NON-OPIOID MECHANISMS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。κ阿片受体激动剂已被证明可以减弱可卡因诱导的可卡因寻求行为的恢复，但对这些模型中单独使用κ受体激动剂的影响知之甚少。该子项目的目的是评价预激注射κ阿片受体激动剂恢复松鼠猴可卡因寻求行为的能力，并将这些药物的作用与μ和δ阿片受体激动剂的作用进行比较。受试者接受训练，自我管理静脉注射可卡因下的二阶时间表，其中药物寻求维持联合可卡因注射和可卡因配对的视觉刺激。在随后的消退会议上，生理盐水代替可卡因和可卡因配对刺激被省略。在测试过程中，只有盐水可用于自我管理，但可卡因配对刺激的反应-视情况而定的介绍被恢复。可卡因注射引发剂量依赖性恢复药物寻求。启动注射κ阿片激动剂依那多林、螺多林和GR 89，696也以剂量相关的方式恢复可卡因寻求行为，而启动注射μ阿片激动剂海洛因、吗啡和芬太尼以及δ阿片激动剂SNC 80不能恢复药物寻求。用纳洛酮或κ阿片受体拮抗剂nor-binaltorphimine预处理不会减弱κ激动剂的引发诱导作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Kappa opioid agonists have been shown to attenuate the reinstatement of cocaine-seeking behavior induced by priming injections of cocaine, but relatively little is known about the effects of kappa agonists alone in these models. The objective of this subproject was to evaluate the ability of priming injections of kappa opioid agonists to reinstate cocaine-seeking behavior in squirrel monkeys and to compare the effects of these drugs with the actions of mu and delta opioid agonists. Subjects were trained to self-administer intravenous cocaine under a second-order schedule in which drug seeking was maintained jointly by cocaine injections and a cocaine-paired visual stimulus. In subsequent extinction sessions, saline was substituted for cocaine and the cocaine-paired stimulus was omitted. During test sessions only saline was available for self-administration but response-contingent presentations of the cocaine-paired stimulus were restored. Priming injections of cocaine induced dose-dependent reinstatement of drug seeking. Priming injections of the kappa opioid agonists enadoline, spiradoline and GR89,696 also reinstated cocaine-seeking behavior in a dose-related manner, whereas priming injections of the mu opioid agonists heroin, morphine and fentanyl and the delta opioid agonist SNC 80 did not reinstate drug seeking. Pretreatment with naltrexone or the kappa opioid receptor antagonist nor-binaltorphimine did not attenuate the priming-induced effects of kappa agonists.