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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。Kappa阿片类激动剂已被证明可以减轻可卡因启动注射引起的可卡因寻求行为的恢复，但相对而言，在这些模型中，Kappa激动剂单独使用的效果知之甚少。本子项目的目的是评估启动注射kappa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mu和delta阿片受体激动剂的作用进行比较。受试者被训练在二级计划下自行静脉注射可卡因，在二级计划中，通过可卡因注射和可卡因配对的视觉刺激来维持药物寻求。在随后的消退阶段，用生理盐水代替可卡因，并省略可卡因配对刺激。在测试期间，只有生理盐水可用于自我给药，但可卡因配对刺激的反应偶然呈现被恢复。可卡因启动注射诱导剂量依赖性药物寻求恢复。阿片受体激动剂依纳多林、螺旋多林和GR89,696的启动注射也以剂量相关的方式恢复可卡因寻求行为，而阿片受体激动剂海洛因、吗啡和芬太尼的启动注射和阿片受体激动剂snc80没有恢复药物寻求行为。用纳曲酮或kappa阿片受体拮抗剂（非- binaltorphamine）预处理不会减弱kappa激动剂的启动诱导作用。

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.