Abstract

ABSTRACT The role of duration of action on the relative reinforcing effects of three opioid drugs (fentanyl, alfentanil, and remifentanil) was evaluated. Duration and onset of action were determined using measures of respiratory depression and antinociception after i.v. administration. Effects on minute volume of respiration indicated that each of the three opioids had immediate onsets of action after i.v. administration. Fentanyl's duration of suppression of respiration and antinociception was longer than that of alfentanil, which was longer than that of remifentanil. Reinforcing strength was measured in i.v. self-administration studies in which the fixed ratio resulting in drug administration was increased from one session to the next. Comparisons were made of the behavioral economic variables P max and area under the demand curve (O max ). Remifentanil maintained higher rates of responding than did alfentanil, and alfentanil maintained higher rates of responding than did fentanyl. When normalized demand functions were compared, however, the drugs did not differ significantly from each other in terms of P max or O max . These data agree with those of others who have suggested that duration of action is not an important contributor to drugs' reinforcing strength. Relatively little is known about what properties of drugs of abuse contribute to their reinforcing effects. It is generally acknowledged, however, that stimuli function better as reinforcers if there is relatively little delay between the response and reinforcer delivery These latter three drugs vary in their durations as well as their onsets of action, and the contribution of duration of action to the relative reinforcing effects of drugs of abuse is not well documented. Drugs that act at the -opioid receptor are a natural choice for experimental procedures designed to evaluate the role of duration of drug action on reinforcing strength. There are several -opioid agonists that vary almost exclusively in their pharmacokinetics. Fentanyl is a fairly long-acting -opioid agonist, alfentanil has a nearly identical profile of activity but with a shorter duration of action, and remifentanil is an ultrashort-acting -opioid agonist, useful in surgical procedures in which it can be administered by constant infusion Materials and Methods Subjects Eleven adult male and female rhesus monkeys (Macaca mulatta) with body weights ranging between 5.4 and 12.8 kg were used. They