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Reinforcing effect of alfentanil is mediated by mu opioid receptors: apparent pA2 analysis
1Department of Psychology, University of Michigan, Ann Arbor 48109-0626.
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.
Insights
Alfentanil, a short-acting opioid agonist, reinforces operant behavior in rhesus monkeys, likely by activating mu-opioid receptors. This was confirmed by the opioid antagonist quadazocine
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Opioid agonists are known to influence operant behavior.
- Understanding the specific receptor subtypes involved is crucial for developing targeted therapeutics.
Purpose of the Study:
- To investigate whether the short-duration opioid agonist, alfentanil, acts at mu-opioid receptors to positively reinforce operant behavior in rhesus monkeys.
Main Methods:
- Apparent pA2 analysis and Schild Plot analysis were employed.
- Rhesus monkeys were trained to lever-press for alfentanil injections under a fixed-ratio schedule.
- The effects of the opioid antagonist quadazocine on alfentanil's dose-response curve were examined.
Main Results:
- Alfentanil produced dose-dependent increases in response rates, reaching 3.05 responses/sec at the highest dose.
- Quadazocine caused dose-dependent, parallel rightward shifts in the alfentanil dose-response curve.
- Schild analysis yielded an apparent pA2 value of 7.6 for quadazocine, consistent with mu-receptor interaction.
Conclusions:
- The findings strongly suggest that mu-opioid receptors mediate the positive reinforcing effects of alfentanil in operant behavior.
- The results contribute to understanding the neurobiological basis of opioid reinforcement.