Discriminative stimulus effects of enadoline in pigeons

Michael R. Brandt, Charles P. France

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The discriminative stimulus effects of enadoline were characterized in pigeons responding under a fixed-ratio 20 schedule of food presentation and discriminating between intramuscular injections of the κ opioid agonist enadoline and saline. Cumulative doses of enadoline dose-dependently increased drug-key responding with the training dose of enadoline (0.178 mg/kg) producing ≤90% drug key responding (% DR). In time course studies, doses of enadoline larger than 0.32 mg/kg produced ≤90% DR for more than 40 min. Naltrexone antagonized both the discriminative stimulus and the rate- decreasing effects of enadoline (pA2 = 6.79 and 6.73, respectively); in some pigeons, naltrexone produced an unsurmountable antagonism of the enadoline discriminative stimulus. Substitution tests using the κ agonists U-50,488, spiradoline, U-69,593 and ethylketocyclazocine resulted in ≤90% DR in most, but not all, pigeons; at larger doses, all compounds markedly decreased response rates. Up to rate-decreasing doses, nalorphine, dynorphin A(1-13) amide (DYN), nalbuphine, butorphanol, morphine and ketamine failed to occasion ≤90% DR; nalbuphine, nalorphine, butorphanol, but not DYN, antagonized the discriminative stimulus and the rate-decreasing effects of enadoline. This study established stimulus control with enadoline in pigeons and results from substitution studies in these pigeons support the view that the enadoline discriminative stimulus is mediated by κ opioid receptors; these results further demonstrate that nalbuphine and butorphanol have κ antagonist actions in pigeons. The negative results obtained with DYN are in contrast to previous demonstrations of κ agonist effects for DYN and might provide support for the hypothesized importance of nonopioid systems in the effects of this peptide.

Original languageEnglish (US)
Pages (from-to)960-967
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume277
Issue number2
StatePublished - May 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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