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

 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.