SUBJECTIVE EFFECTS OF COCAINE AND HEROIN: OPIOID RECEPTOR 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。许多多种药物滥用者将可卡因和海洛因以“速丸”的形式一起服用。先前的研究发现，海洛因可以增强可卡因的行为效果，尽管这种增强的受体机制尚不清楚。本研究研究了在固定比例的食物递送计划下，训练恒河猴区分静脉注射可卡因和生理盐水，研究了mu和delta阿片受体机制在快速球组合主观效应中的相对作用。在替代研究中，阿片受体激动剂海洛因和美沙酮部分重现了可卡因的主观效应，而阿片受体激动剂snc80则没有。可卡因和海洛因联合治疗，在保持剂量比不变的情况下，同时注射增加剂量的可卡因和海洛因，增强了低至中剂量可卡因的效果，导致可卡因剂量反应函数整体向左移动。与美沙酮联合使用，也观察到可卡因的主观效应有类似的增强。相比之下，snc80与可卡因联合使用导致可卡因剂量-反应函数的形状和位置变化不太明显。在其他研究中，海洛因的可卡因增强作用被低剂量的阿片受体拮抗剂纳曲酮完全逆转；但不是阿片受体拮抗剂纳尔trindo

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. Many polydrug abusers take cocaine in combination with heroin by administering the drugs together in the form of a "speedball". Previous studies have found that heroin can enhance the behavioral effects of cocaine, although the receptor mechanisms underlying this enhancement are not well understood. The present study investigated the relative role of mu and delta opioid receptor mechanisms in the subjective effects of speedball combinations in rhesus monkeys trained to discriminate intravenous injections of cocaine from saline under a fixed-ratio schedule of food delivery. In substitution studies, the mu opioid receptor agonists heroin and methadone partially reproduced the subjective effects of cocaine, whereas the delta opioid receptor agonist SNC 80 did not. Combined treatment with cocaine and heroin, administered by co-injecting incremental doses of cocaine and heroin while keeping the dose-ratio constant, enhanced the effects of low-to-intermediate doses of cocaine, resulting in an overall leftward shift in the cocaine dose-response function. A similar enhancement of the subjective effects of cocaine was observed with co-administration of methadone. In contrast, co-administration of SNC 80 with cocaine resulted in a less pronounced change in the shape and position of the cocaine dose-response function. In additional studies, the cocaine-enhancing effects of heroin were reversed completely by low doses of the mu opioid receptor antagonist naltrexone; but not by the delta opioid receptor antagonist naltrindo