Reinforcing effect of alfentanil is mediated by mu opioid receptors: Apparent pA2 analysis

Abstract

Apparent pA2 analysis was used to determine whether the short-duration opioid agonist, alfentanil, acts at mu receptors in the positive reinforcement of operant behavior in the rhesus monkey. In test sessions a red light signaled the availability of alfentanil injections. If a monkey pressed a response lever 30 times, a specific dose of alfentanil was injected i.v., and the red light was extinguished for 10 min. This cycle could be repeated for up to 130 min, the maximum length of a session. Between successive test sessions at least three maintenance sessions were held; in these sessions injections of 0.32 mg/kg/injection of codeine were made available. The dose of alfentanil was changed from one test session to the next, and dose-dependent changes in rates of responding resulted. Rates reached 3.05 responses/sec at 0.010 mg/kg/injection, the highest dose tested. The opioid antagonist, quadazocine, produced dose-dependent, parallel shifts to the right in the alfentanil dose-response curve. In Schild Plot analysis the regression line fit to the antagonism data had a slope of -1.1; the apparent pA2 value for quadazocine was 7.6. This value was close to apparent pA2 values obtained with mu agonists in studies of other behavioral effects of opioids, but distinct from values obtained with kappa agonists in those studies. Thus, it is likely that mu receptors mediate the positive reinforcing effect of alfentanil.