DISCRIMINATIVE STIMULUS EFFECTS OF ENADOLINE IN PIGEONS

The discriminative stimulus effects of enadoline were characterized in pigeons responding under a fixed-ratio 20 schedule of food presentati on and discriminating between intramuscular injections of the kappa op ioid agonist enadoline and saline. Cumulative doses of enadoline dose- dependently increased drug-key responding with the training dose of en adoline (0.178 mg/ kg) producing greater than or equal to 90% drug key responding (% DR). In time course studies, doses of enadoline larger than 0.32 mg/kg produced greater than or equal to 90% DR for more than 40 min. Naltrexone antagonized both the discriminative stimulus and t he rate-decreasing effects of enadoline (pA(2) = 6.79 and 6.73, respec tively); in some pigeons, naltrexone produced an unsurmountable antago nism of the enadoline discriminative stimulus. Substitution tests usin g the kappa agonists U-50,488, spiradoline, U-69,593 and ethylketocycl azocine resulted in greater than or equal to 90% DR in most, but not a ll, pigeons; at larger doses, all compounds markedly decreased respons e rates. Up to rate-decreasing doses, nalorphine, dynorphin A(1-13) am ide (DYN), nalbuphine, butorphanol, morphine and ketamine failed to oc casion greater than or equal to 90% DR; nalbuphine, nalorphine, butorp hanol, but not DYN, antagonized the discriminative stimulus and the ra te-decreasing effects of enadoline. This study established stimulus co ntrol with enadoline in pigeons and results from substitution studies in these pigeons support the view that the enadoline discriminative st imulus is mediated by kappa opioid receptors; these results further de monstrate that nalbuphine and butorphanol have kappa antagonist action s in pigeons. The negative results obtained with DYN are in contrast t o previous demonstrations of kappa agonist effects for DYN and might p rovide support for the hypothesized importance of nonopioid systems in the effects of this peptide.