Effect of prazosin and guanfacine on stress-induced reinstatement of alcohol and food seeking in rats.

Rationale and Objectives—Relapse to alcohol use during abstinence or maladaptive eating habits during dieting is often provoked by stress. The anxiogenic drug yohimbine, which causes stress-like responses in humans and nonhumans, reliably reinstates alcohol and food seeking in a rat relapse model. Yohimibine is a prototypical alpha-2 adrenoceptor antagonist but results from studies on noradrenaline's role in yohimbine-induced reinstatement of drug and food seeking are inconclusive. Here we further addressed this issue by studying the effect of the alpha-1 adrenoceptor antagonist prazosin and the alpha-2 adrenoceptor agonist guanfacine on yohimbineinduced reinstatement. Methods—In Exp. 1, we trained rats to self-administer alcohol (12% w/v, 1-h/day) and after extinction of alcohol-reinforced lever-pressing, we tested prazosin's (0.5, 1.0, and 2.0 mg/kg, i.p.) or guanfacine's (0.125, 0.25, and 0.5 mg/kg, i.p.) effect on yohimbine (1.25 mg/kg, i.p.)-induced reinstatement; we also examined prazosin's effect on intermittent-footshock-stress-induced reinstatement. In Exp. 2, we trained food-restricted rats to self-administer 45 mg food pellets and first examined prazosin's or guanfacine's effects on food-reinforced responding, and then, after extinction of lever presses, on yohimibine-induced reinstatement. Results—Prazosin (0.5-2.0 mg/kg) blocked yohimbine-induced reinstatement of food and alcohol seeking, as well as footshock-induced reinstatement of alcohol seeking. Guanfacine attenuated yohimbine-induced reinstatement of alcohol seeking at the highest dose (0.5 mg/kg) but its effect on yohimbine-induced reinstatement of food seeking was not significant. Neither prazosin nor guanfacine affected high rate food-reinforced responding. Conclusions—Results demonstrate an important role of postsynaptic alpha-1 adrenoceptors in stress-induced reinstatement of alcohol and food seeking.