Discriminative stimulus properties of cocaine: enhancement by beta-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 beta-adrenergic receptor antagonists were administered alone or in combination with cocaine (2.5 mg/kg, i.p.) 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 beta 2/beta 1-adrenergic antagonists (-)-propranolol and tertatolol, and the beta 2-adrenergic antagonist, ICI 118,551, produced high-dose appropriate responding in a dose-related manner when administered (i.p.) in combination with the low training dose of cocaine. In contrast, neither the peripheral beta 2/beta 1-adrenergic antagonist, nadolol, nor the central beta 1-adrenergic antagonist, beta-xolol enhanced the behavioral effects of the low dose of cocaine in a manner comparable with that produced by compounds with central beta 2-adrenergic antagonist properties. Also in contrast to findings obtained using beta-adrenergic antagonists, neither the alpha 1-adrenergic agonist cirazoline, nor the alpha 2-adrenergic ligands (+/-)-efaroxan and UK-14304 enhanced the behavioral effects of the low dose of cocaine. Overall, these results suggest that central beta 2-adrenergic receptors may play a modulatory role in the discriminative stimulus effects of cocaine.