Clonidine, the α2-adrenergic receptor agonist which in moderate doses decreases noradrenergic signaling by stimulating inhibitory pre-synaptic α2-adrenergic receptors (Aghajanian & VanderMaelen, 1982; Starke, Montel, Gayk, & Merder, 1974), decreased voluntary alcohol drinking in a dose-dependent manner when administered to P rats for either 2 or 5 consecutive days. These results are consistent with our reports that prazosin, which decreases noradrenergic signaling by blocking post-synaptic α1-adrenergic receptors, decreases alcohol drinking in P rats when administered acutely (Rasmussen et al., 2009) or chronically (Froehlich, Hausauer, Federoff, et al., 2013;). The fact that two different pharmacologic interventions that decrease noradrenergic signaling, but via different mechanisms, are both capable of suppressing alcohol drinking is consistent with evidence that activation of the noradrenergic system plays a key role in mediating voluntary alcohol drinking. These results are also consistent with reports that: a) the α2-adrenergic receptor agonist, lofexidine, reduces operant self-administration of alcohol by Wistar rats (Lé, Harding, Juzytsch, Funk, & Shaham, 2005), b) clonidine and another α2-adrenergic receptor agonist, guanfacine, decrease alcohol drinking by food-restricted rats selectively bred for alcohol drinking (descendants of the Finnish
