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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 (Renner, 1964;de Villiers, 1977). There is some evidence to support the notion that drugs that have fast onsets of action are stronger reinforcers than drugs that have slow onsets of action. Balster and Schuster (1973) and Panlilio et al. (1998), for example, reported that lower rates of behavior were maintained by cocaine when it was delivered slowly compared with more rapid administration. We have found that ketamine, an NMDA antagonist with a rapid onset of action, is as strong a reinforcer as phencyclidine, an NMDA antagonist with a somewhat less rapid onset of action, but much stronger as a reinforcer than dizocilpine, an NMDA antagonist with a slow onset of action (Winger et al., 2002).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. Panlilio and Schindler (2000) are among the few who have compared behavior maintained by shorter and longer acting drugs. They found that the ultrashort-acting opioid remifentanil served as a reinforcer when delivered intravenously to rats and that it maintained breakpoints under progressive ratio schedules that were not markedly different from those maintained by the longer-acting opioid heroin. They concluded that duration of action was independent of the ability to serve as a reinforcer.Drugs that act at the -opioid receptor are a natural choice for experimental procedures designed to evaluate th...

No abstract

That comparable levels of morphine tolerance were obtained in males and females when the functional chronic morphine dose was taken into consideration suggests that the mechanism underlying tolerance is not sex-dependent. Sex differences in the effectiveness of buprenorphine and dezocine when administered acutely and during chronic morphine administration further suggest that these opioids have lower efficacy at the mu opioid receptor in females.