SUBJECTIVE EFFECTS OF COCAINE AND HEROIN: OPIOID RECEPTOR MECHANISMS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。许多吸食多种毒品的人在吸食可卡因和海洛因的同时，以“快球”的形式同时服用这些药物。以前的研究发现，海洛因可以增强可卡因的行为效应，尽管这种增强背后的受体机制还不是很清楚。本研究通过训练恒河猴在固定配餐比例下区分静脉注射可卡因和生理盐水的快球组合，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，Mu阿片受体激动剂海洛因和美沙酮部分复制了可卡因的主观效应，而Delta阿片受体激动剂SNC80不能。通过同时注射递增剂量的可卡因和海洛因，同时保持剂量比恒定，可卡因和海洛因的联合治疗增强了中低剂量可卡因的效果，导致可卡因剂量-反应函数的整体左移。与美沙酮联合给药的可卡因的主观效应也有类似的增强。相比之下，SNC80与可卡因联合给药后，可卡因剂量反应函数的形状和位置发生了不太明显的变化。在另一项研究中，海洛因的可卡因增强效应可被Mu阿片受体拮抗剂纳曲酮完全逆转，但不能被Delta阿片受体拮抗剂纳曲林多逆转。

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