Discriminative stimulus effects of spiradoline, a kappa-opioid agonist

Psychopharmacology (Berl). 1991;105(4):447-52. doi: 10.1007/BF02244362.

Abstract

This study represents the initial step in assessing the discriminative effects of spiradoline (U62,066), a potent congener of the selective kappa-opioid agonist, U50,488. Separate groups of rats were trained to discriminate between SC injections of saline and either 3.0 mg/kg spiradoline or 3.0 mg/kg morphine in a discrete-trial shock-avoidance/escape procedure. Spiradoline-trained rats generalized completely to U50,488 (ED50S for spiradoline and U50,488 were 0.66 and 8.71 mg/kg, respectively), but selected the choice lever appropriate for saline in generalization tests with graded doses of morphine, phencyclidine, and agonist-antagonist opioids with varying degrees of kappa activity, ethylketocyclazocine, nalorphine, and butorphanol. Morphine-trained rats did not generalize to spiradoline. Naltrexone (0.01 or 0.1 mg/kg) blocked surmountably the discriminative effects of both spiradoline and morphine, but was approximately 10-fold less potent against spiradoline. These results indicate that the discriminative effects of spiradoline are mediated by kappa-opioid receptors; meaningful mu-opioid and PCP/sigma components of action were not in evidence. The potency and apparent pharmacological selectivity of spiradoline suggest the potential value of this drug for studying kappa-opioid-mediated stimulus control of behavior.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Animals
  • Butorphanol / pharmacology
  • Discrimination, Psychological / drug effects*
  • Discrimination, Psychological / physiology
  • Ethylketocyclazocine / pharmacology
  • Generalization, Stimulus
  • Male
  • Morphine / pharmacology
  • Nalorphine / pharmacology
  • Phencyclidine / pharmacology
  • Pyrrolidines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Reaction Time
  • Receptors, Opioid / drug effects*
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu

Substances

  • Pyrrolidines
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Ethylketocyclazocine
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Morphine
  • Phencyclidine
  • spiradoline
  • Butorphanol
  • Nalorphine