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


OBJECTIVE
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 micrograms/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 micrograms/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.
Panlilio
L V
LV
Preclinical Pharmacology Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA. lpanlili@intra.nida.nih.gov
Schindler
C W
CW
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003932:Heroin / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists; D012055:Reinforcement Schedule; D000077208:Remifentanil; D012646:Self Administration / Q000523:psychology
D000701:Analgesics, Opioid; D010880:Piperidines; D017450:Receptors, Opioid, mu; D003932:Heroin; D000077208:Remifentanil