Role of delta receptor efficacy as a determinant of delta/mu opioid interactions in rhesus monkeys

Abstract

Delta opioid agonists have been reported to selectively enhance the antinociceptive effects of mu opioid agonists without enhancing other, potentially untoward mu agonist effects such as sedation, respiratory depression or abuse potential. The purpose of the present study was to examine the role of delta receptor efficacy as a determinant of delta/mu interactions in rhesus monkeys in two different behavioral procedures: (a) an assay of schedule‐controlled responding maintained by food reinforcement, and (b) an assay of thermal nociception. The effects of the selective mu agonist fentanyl were examined in combination with the high‐efficacy delta agonist SNC243A, the intermediate‐efficacy agonist MSF61, or the delta antagonist naltrindole. Fentanyl was tested in combination with three different proportions of each delta opioid. Fentanyl/SNC243A interactions were superadditive in the assay of antinociception and additve in the assay of schedule‐controlled responding. Fentanyl/MSF61 interactions were additive in both procedures, and fentanyl/naltrindole interactions were additive or subadditive in both procedures. These results suggest that high efficacy at delta receptors is required for synergistic delta/mu interactions in assays of antinociception in rhesus monkeys. Supported by R01 DA11460 from NIDA/NIH.