Self-administration of cocaine-remifentanil mixtures by monkeys: an isobolographic analysis
Woolverton WL, Wang Z, Vasterling T, Tallarida R.
Division of Neurobiology and Behavior Research,
Department of Psychiatry and Human Behavior,
University of Mississippi Medical Center,
2500 N. State Street, Jackson, MS, 39216, USA,
Psychopharmacology (Berl). 2008 May 8


RATIONALE: Abuse 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. OBJECTIVES: The objectives of the present experiment were to allow monkeys to self-administer mixtures of cocaine and the mu 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 METHODS: Rhesus 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 ED(50)s. Results were analyzed using isobolographic techniques. RESULTS: Both 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. CONCLUSIONS: Combinations 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.
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