Involvement of the α₁-adrenergic receptor in caffeine-induced drug discrimination and conditioned taste avoidance in...

The present experiments determined the role of the α₁-adrenergic receptor in mediating the behavioral actions of caffeine in rats utilizing two different paradigms: drug discrimination (DD) and conditioned taste avoidance (CTA). After rats achieved response proficiency (80% caffeine-appropriate responding) with caffeine (30 mg/kg) during DD training, rats underwent stimulus generalization tests in which rats were administered vehicle (0.5% gum Arabic) or modafinil (5, 10 or 20 mg/kg) 30 min prior to the session, as determined by a Latin-Square design. In the CTA experiment, two conditioning sessions occurred 48-h apart in which rats received 15 min access to salt water (0.6%) followed immediately by an injection of vehicle (distilled water) or prazosin (0.5, 1.0, or 2.0 mg/kg) and then 5 min later a second injection of vehicle (physiological saline) or caffeine (30 mg/kg). The test session occurred 96 h after the last conditioning session. The α₁-adrenergic agonist, modafinil, dose-dependently generalized to caffeine. The selective α₁-adrenergic antagonist, prazosin, dose-dependently potentiated caffeine-induced CTA. Taken together, these results suggest that the α₁-adrenergic receptor system contributes to the behavioral actions of a moderate caffeine dose.