Stimulation of α2-adrenergic receptors in the central nucleus of the amygdala attenuates stress-induced reinstatement of nicotine seeking in rats

Tobacco addiction is a chronic disorder that is characterized by craving for tobacco products, withdrawal upon smoking cessation, and relapse after periods of abstinence. Previous studies demonstrated that systemic administration of alpha 2-adrertergic receptor agonists attenuates stress-induced reinstatement of drug seeking in rats. The aim of the present experiments was to investigate the role of noradrenergic transmission in the central nucleus of amygdala (CeA) in stress-induced reinstatement of nicotine seeking. Rats self-administered nicotine for 14-16 days and then nicotine seeking was extinguished by substituting saline for nicotine. The effect of the intra-CeA infusion of the alpha 2-adrenergic receptor agonists clonidine and dexmedetomidine, the nonselective beta 1/beta 2-adrenergic receptor antagonist propranolol, and the alpha 1-adrenergic receptor antagonist prazosin on stress-induced reinstatement of nicotine seeking was investigated. In all the experiments, exposure to footshocks reinstated extinguished nicotine seeking. The administration of clonidine or dexmedetomidine into the CeA attenuated stress-induced reinstatement of nicotine seeking. The administration of propranolol or prazosin into the CeA did not affect stress-induced reinstatement of nicotine seeking. Furthermore, intra-CeA administration of clonidine or dexmedetomidine did not affect operant responding for food pellets. This suggests that the effects of clonidine and dexmedetomidine on stress-induced reinstatement of nicotine seeking were not mediated by motor impairments or sedation. Taken together, these findings indicate that stimulation of alpha 2-adrenergic receptors, but not blockade of alpha 1 or beta-adrenergic receptors, in the CeA attenuates stress-induced reinstatement of nicotine seeking. These findings suggest that alpha 2-adrenergic receptor agonists may at least partly attenuate stress-induced reinstatement of nicotine seeking by stimulating alpha 2-adrenergic receptors in the CeA. (C) 2010 Elsevier Ltd. All rights reserved.