Self-administration of cocaine-remifentanil mixtures by monkeys: an isobolographic analysis.
Self-administration of cocaine-remifentanil mixtures by monkeys: an isobolographic analysis.
复制标题
猴子自行施用可卡因-瑞芬太尼混合物：等辐射线分析。
DOI：
10.1007/s00213-008-1152-5
复制
发表时间：
2008
影响因子：
3.4
通讯作者：
Tallarida,Ronald
中科院分区：
文献类型：
--
作者：
Woolverton,WL;Wang,Zhixia;Vasterling,Theresa;Tallarida,Ronald
RationaleAbuse of mixtures of stimulants and opioids (“speedball”) is common. Although this combination has been studied in the laboratory, conclusions about the nature of the cocaine/opioid interaction have been mixed.ObjectivesThe objectives of the present experiment were to allow monkeys to self-administer mixtures of cocaine and the μ opioid agonist remifentanil and to quantify the interaction using the isobolographic approach. Our hypothesis was that the drugs would be super-additive in their reinforcing effects.Materials and methodsRhesus monkeys (n= 5) prepared with i.v. catheters were allowed to self-administer cocaine or saline under a progressive-ratio schedule. When responding was stable, doses of cocaine or remifentanil were made available in test sessions. Next, mixtures of doses of the drugs were tested over a range of doses in 1:1, 1:2, and 2:1 ratios of their ED50s. Results were analyzed using isobolographic techniques.ResultsBoth drugs alone and all drug mixtures functioned as positive reinforcers in a dose-related manner. Cocaine maintained more responding at maximum than did remifentanil, i.e., was a stronger reinforcer. The experimentally determined equi-effective dose for the 1:1 and 1:2 cocaine/remifentanil mixtures tended toward super-additivity, but the difference from additivity did not achieve statistical significance. The 2:1 mixture was super-additive. Maximum responding maintained by the mixtures was higher than that maintained by remifentanil but not different from cocaine.ConclusionsCombinations of cocaine and remifentanil can be additive or super-additive as positive reinforcers, depending on proportions of each. Interactions between stimulants and opioids may contribute to the abuse of these mixtures.
