Self-administration of cocaine-opioid combinations by rhesus monkeys:: Evaluation of the role of μ receptor efficacy using Labor supply analysis
Self-administration of cocaine-opioid combinations by rhesus monkeys:: Evaluation of the role of μ receptor efficacy using Labor supply analysis
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DOI：
10.1124/jpet.104.076646
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发表时间：
2005-03-01
影响因子：
3.5
通讯作者：
Spealman, RD
中科院分区：
文献类型：
--
作者：
Rowlett, JK;Rodefer, JS;Spealman, RD
可卡因和海洛因经常被滥用，自我管理的药物组合作为一种“快球”。我们评估了Mu阿片受体的内在效应对可卡因-阿片类药物联合给药的影响程度，并使用名为“劳动力供应”的行为经济学模型来定量评估可卡因-阿片联合用药的强化效果。对恒河猴(n=8)进行静脉注射递增比训练。可卡因注射，在实验期间反应要求增加，初始反应要求不同。与单独使用毒品相比，可卡因和海洛因的联合使用增强了自我给药，当两种药物联合使用时，无效剂量的两种药物仍保持自我给药。高效的MU激动剂阿芬太尼和低效的激动剂纳布芬也观察到了这些效果。使用劳动力供给经济模型，发现海洛因、阿芬太尼或纳布芬与相对较低剂量的可卡因联合使用可以增加每次注射的次数(“收入”)和每次注射的总反应(“工作”)。将相对较高剂量的可卡因与海洛因或阿芬太尼结合使用，但不与纳布芬联合使用，也只会导致伴随着劳动力增加而出现的收入小幅减少，这表明海洛因和阿芬太尼使可卡因消费对增加的反应成本更具抵抗力，或者更缺乏弹性。总而言之，这些发现表明，即使在u阿片受体的内在效力水平相对较低的情况下，也可能发生速球自我给药，药物消耗和劳动之间的非弹性关系可能有助于速球滥用的持续。
Cocaine and heroin often are abused by self-administering the drugs in combination as a "speedball". We evaluated the extent to which intrinsic efficacy at the mu-opioid receptor influences combined cocaine-opioid self-administration and used the behavioral economic model termed "labor supply" to quantitatively evaluate the reinforcing effects of cocaine- opioid combinations. Rhesus monkeys ( n = 8) were trained under a progressive-ratio schedule of i.v. cocaine injection in which the response requirement increased during the experimental session and the initial response requirement was varied. Combination of cocaine with heroin enhanced self-administration compared with the drugs individually, with ineffective doses of both drugs maintaining self-administration when combined. These effects also were observed with the high-efficacy mu agonist alfentanil and low-efficacy agonist nalbuphine. Using the labor supply economic model, combinations of heroin, alfentanil, or nalbuphine with relatively low doses of cocaine were found to increase the number of injections per session ("income") and total responses per session ("labor"). Combination of a relatively high dose of cocaine with either heroin or alfentanil, but not nalbuphine, also resulted in only a small reduction in income concomitant with increased labor, suggesting that heroin and alfentanil made cocaine consumption more resistant to increasing response costs, or more "inelastic." Collectively, these findings suggest that speedball self-administration may occur even with relatively low levels of intrinsic efficacy at mu-opioid receptors and that an inelastic relationship between drug consumption and labor may contribute to the persistence of speedball abuse.