DISCRIMINATIVE STIMULUS EFFECTS OF THE MIXED-OPIOID AGONIST ANTAGONIST DEZOCINE - CROSS-SUBSTITUTION BY MU-OPIOID AND DELTA-OPIOID AGONISTS/

The purpose of this investigation was to evaluate the discriminative s timulus effects of the mixed-opioid agonist/antagonist dezocine. In pi geons trained to discriminate 1.7 mg/kg dezocine from saline, a series of opioids with activity at the mu opioid receptor substituted comple tely for the dezocine stimulus with a rank order of potency similar to that obtained in other assays sensitive to the effects of mu agonists (i.e., fentanyl > [-]-cyclazocine > buprenorphine = butorphanol > 1-m ethadone > nalbuphine > [-]-metazocine > morphine). (-)-N-allyl-normet azocine and (+)-propoxyphene substituted partially for the dezocine st imulus, an effect obtained even when tested up to doses that suppresse d responding. Naloxone (0.1 - 10 mg/kg) antagonized the stimulus effec ts of dezocine, (+)-propoxyphene and fentanyl in a dose-related manner , whereas doses of naloxone that antagonized fentanyl's rate-decreasin g effects failed to antagonize the rate-decreasing effects of dezocine and (+)-propoxyphene. A 10-mg/kg dose of the mu-selective, noncompeti tive antagonist beta-funaltrexamine was more effective against the sti mulus effects of dezocine and nalbuphine than against morphine and fen tanyl. As was observed with naloxone, beta-funaltrexamine failed to an tagonize dezocine's rate-decreasing effects. The delta agonists BW373U 86 and SNC80 substituted partially for the dezocine stimulus, and thes e effects were reversed by doses of the delta-selective antagonist nal trindole (0.1 and 1.0 mg/kg) that had no effect on the dezocine stimul us. Naltrindole also antagonized the rate-decreasing effects produced by BW373U86 and SNC80, but not those of dezocine. The kappa agonists b remazocine, spiradoline, U50,488 and U69,593 failed to substitute for the dezocine stimulus. The kappa-selective antagonist norbinaltorphimi ne (1.0 mg/kg) failed to antagonize dezocine's stimulus or rate-decrea sing effects. The present findings indicate that dezocine shares simil ar stimulus effects with both mu and delta agonists, its stimulus effe cts are reversed by mu-selective antagonists, and its rate-decreasing effects are not mediated by activity at mu, kappa or delta opioid rece ptors.