Characterization of the reinforcing effects of the mixed‐action mu/delta opioid agonist MMP2200 using the drug self‐administration procedure in rats

Prescription mu opioid pain relievers (e.g., morphine, fentanyl) are among the most widely prescribed drugs used to treat pain. However, these drugs also produce deleterious side effects including respiratory depression, abuse liability and drug dependence. Our laboratory is currently evaluating the reinforcing effects of a series of mixed‐action mu/delta opioid receptor compounds. This study characterized the reinforcing effects of the mu/delta opioid receptor agonist MMP2200 using the drug self‐administration procedure. Rats were trained to respond for 0.0032 mg/kg/infusion of fentanyl on an FR5 schedule of reinforcement. Once stable patterns of self‐administration were established, complete dose‐effect curves for fentanyl (0.00032‐0.01 mki), MMP2200 (0.032‐1 mki) and morphine (0.01–0.32 mki) were determined. The dependent measures were number of infusions, and cumulative latencies to first three reinforcers. Rats reliably self‐administered fentanyl and morphine. In contrast, rats showed variable self‐administration of MMP2200. Peak doses of fentanyl and morphine maintained higher response rates than the peak dose of MMP2200. Relative to fentanyl and morphine, cumulative latencies to first three reinforcers for MMP2200 were longer and similar to saline. These data suggest that MMP2200 may be less reinforcing than fentanyl or morphine.