Discriminative stimulus properties of cocaine: enhancement by ββ-adrenergic receptor antagonists

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 β₂/β₁-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 β₂/β₁-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.