If alcohol drinking is due in part to activation of the noradrenergic system, any drug that decreases noradrenergic signaling might be expected to decrease alcohol drinking. We recently determined that combined treatment of P rats with both prazosin and propranolol (which block α1- and β-adrenergic receptors, respectively) decreased alcohol drinking more effectively than treatment with either drug alone (Rasmussen, Beckwith, Kincaid, & Froehlich, 2014), suggesting that α1- and β-adrenergic receptors may have complementary roles in facilitating alcohol drinking. This suggests that administration of an α2-adrenergic receptor agonist such as clonidine, which can decrease noradrenergic signaling by decreasing norepinephrine release from presynaptic terminals (Aghajanian & VanderMaelen, 1982; Starke, Montel, Gayk, & Merder, 1974) and thus decrease the amount of norepinephrine available for binding to either α1- or β-adrenergic post-synaptic receptors, may be especially effective in decreasing alcohol drinking. Accordingly, in the present study we evaluated the effect of clonidine on voluntary alcohol drinking in selectively bred alcohol-preferring (P) rats.
