Varenicline Ameliorates Nicotine Withdrawal-Induced Learning Deficits in C57BL/6 Mice

Varenicline, a partial agonist for α4β2 nicotinic acetylcholine receptors (nAChRs) and full agonist for α7 nAChRs, has been approved for the treatment of smoking cessation. Although recent clinical trials support the efficacy of varenicline for managing global nicotine withdrawal symptoms and for smoking cessation, its effects on animal models of specific withdrawal-associated behaviors have not been tested. The present study evaluated the effects of varenicline on contextual fear conditioning and its effects on nicotine (6.3 mg/kg/day) withdrawal-induced deficits in contextual fear conditioning. Varenicline (0.01, 0.1, 1.0 mg/kg) had no effect on contextual fear conditioning when administered alone, but (0.1 mg/kg) prevented nicotine withdrawal-associated deficits in contextual fear conditioning. These data demonstrate, for the first time, that varenicline reverses nicotine withdrawal-induced deficits in an animal model and suggest that varenicline may be effective at treating nicotine withdrawal-associated deficits in learning and memory.