Self-administration of remifentanil, an ultra-short acting opioid, under continuous and progressive-ratio schedules of reinforcement in rats

Rationale: Remifentanil is a mu-opioid agonist with an exceptionally short duration of action. Evaluating remifentanil's effects within the self-administration model of drug abuse may provide insight into the relationship between a drug's duration of action and its effectiveness as a reinforcer. Objectives: This study was conducted to establish a dose-effect function for intravenous remifentanil self-administration in rats and to assess the drug's ability to maintain responding under intermittent schedules of reinforcement. Methods: Inter-infusion intervals were recorded under two continuous-reinforcement schedules of remifentanil self-administration. In the fixed-dose schedule, the unit dose (0.25-32 mu g/kg) was held constant within sessions but varied across sessions. In the variable-dose schedule, four different doses were self-administered in random order within each session. For comparison, heroin (6.25-125 mu g/kg) was studied with the variable-dose schedule. Remifentanil and heroin were also compared under a progressive-ratio schedule of reinforcement in which the response requirements increased exponentially with each successive infusion until responding ceased within each session. Results: Under the continuous-reinforcement schedules, inter-infusion intervals for both drugs increased monotonically as a function of dose, with the remifentanil curve being considerably flatter. Under the progressive-ratio schedule, breaking points varied as an inverted-U shaped function, and the highest breaking points maintained by remifentanil and heroin were similar. At the doses that maintained the highest breaking points under the progressive-ratio schedule, post-infusion pauses under the continuous-reinforcement schedule were about three times shorter with remifentanil than with heroin. Conclusions: Although rates of self-administration are clearly influenced by a drug's duration of action, the ability to maintain responding under intermittent schedules of reinforcement may be independent of duration of action.