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

Abstract

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 stressinduced 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.

Role of the kappa-opioid receptor system in stress-induced reinstatement of nicotine seeking in rats

“…Individuals exposed to high levels of stress are more likely to relapse (Bruijnzeel and Gold, 2005). This is supported by the results of studies in laboratory animals showing that exposure to stress can reinstate nicotine seeking following extinction of operant responding (Buczek et al, 1999; Martin-García et al, 2009; Yamada and Bruijnzeel, 2011; Zislis et al, 2007). Animals trained to self-administer nicotine also display long-lasting increases in their responsivity to stress (Chen et al, 2008).…”

The Role of Guanfacine as a Therapeutic Agent to Address Stress-Related Pathophysiology in Cocaine-Dependent Individuals

“…In a slightly later study, Glassman and colleagues also showed that clonidine was significantly efficacious in reducing nicotine withdrawal and promoting smoking cessation in women as compared to men (Covey & Glassman, 1991; Glassman et al, 1988), and particularly in vulnerable women (Glassman et al, 1993). Recent preclinical research holds support for these studies showing that intra central nucleus of the amygdala (CeA) infusion of clonidine and dexmedetomidine in rats, attenuates stress-induced reinstatement of nicotine seeking, possibly via synaptic connections between noradrenergic terminals and CRF neurons (Yamada & Bruijnzeel, 2011). …”

Alcohol, Nicotine, and Iatrogenic Withdrawals in the ICU

“…Neither bupropion nor varenicline, agents believed to modulate nicotine withdrawal symptoms and used to enhance the effectiveness of smoking cessation (125), have been studied in an ICU context. Others avenues are promising, such as the a^-adrenergic receptor agonists, dexmedetomidine and clonidine, have benefits in attenuating stress-induced nicotine craving in animal and human models (126)(127)(128) but clinical studies as to their effectiveness and safety are currently lacking.…”