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 α2-adrenergic 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 α2-adrenergic receptor agonists clonidine and dexmedetomidine, the nonselective β1/β2-adrenergic receptor antagonist propranolol, and the α1-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 α2-adrenergic receptors, but not blockade of α1 or β-adrenergic receptors, in the CeA attenuates stress-induced reinstatement of nicotine seeking. These findings suggest that α2-adrenergic receptor agonists may at least partly attenuate stress-induced reinstatement of nicotine seeking by stimulating α2-adrenergic receptors in the CeA.
Yamada
Hidetaka
H
Department of Psychiatry, McKnight Brain Institute, University of Florida, 100 S Newell Dr, Gainesville, FL 32610, USA.
Bruijnzeel
Adrie W
AW
D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D016739:Behavior, Addictive / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012646:Self Administration; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D014029:Tobacco Use Disorder / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control
D058647:Adrenergic alpha-2 Receptor Agonists; D018341:Receptors, Adrenergic, alpha-2; D009538:Nicotine