Discriminative stimulus properties of cocaine: Enhancement by β- adrenergic receptor antagonists

Mark S. Kleven, Wouter Koek

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Although many of the behavioral effects of cocaine are widely believed to be mediated by blockade of dopamine transporters, recent studies suggest that norepinephrine (NE) may play a modulatory role. In this study, selective and nonselective β-adrenergic receptor antagonists were administered alone or in combination with cocaine (2.5 mg/kg, IP) to rats trained to discriminate a low dose (2.5 mg/kg) from a high dose of cocaine (10 mg/kg) in a two-lever, FR10 drug discrimination procedure. The central β21- adrenergic antagonists (-)-propranolol and tertatolol, and the β2- adrenergic antagonist, ICI 118,551, produced high-dose appropriate responding in a dose-related manner when administered (IP) in combination with the low training dose of cocaine. In contrast, neither the peripheral β21- adrenergic antagonist, nadolol, nor the central β1-adrenergic antagonist, betaxolol enhanced the behavioral effects of the low dose of cocaine in a manner comparable with that produced by compounds with central β2- adrenergic antagonist properties. Also in contrast to findings obtained using β-adrenergic antagonists, neither the α1-adrenergic agonist cirazoline, nor the α2-adrenergic ligands (±)-efaroxan and UK-14304 enhanced the behavioral effects of the low dose of cocaine. Overall, these results suggest that central β2-adrenergic receptors may play a modulatory role in the discriminative stimulus effects of cocaine.

Original languageEnglish (US)
Pages (from-to)307-312
Number of pages6
JournalPsychopharmacology
Volume131
Issue number3
DOIs
StatePublished - Jul 18 1997
Externally publishedYes

Keywords

  • (-)-Propranolol
  • Betaxolol
  • Cocaine
  • Dose versus dose discrimination
  • Drug discrimination
  • ICI 118,551
  • Nadolol
  • Tertatolol
  • β-Adrenergic receptors

ASJC Scopus subject areas

  • Pharmacology

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