Varenicline ameliorates ethanol-induced deficits in learning in C57BL/6 mice

Ethanol is a frequently abused drug that impairs cognitive processes such as learning. Varenicline, an alpha 4 beta 2 nicotinic receptor partial agonist and alpha 7 nicotinic receptor full agonist prescribed for smoking cessation, has been shown to decrease ethanol consumption. The current study investigated whether varenicline could ameliorate ethanol-induced deficits in learning and whether varenicline alters blood alcohol concentration in C57BL/6 mice. Conditioning consisted of two auditory conditioned stimulus (CS; 30 s, 85 dB white noise)-foot shock unconditioned stimulus (US; 2 s, 0.57 mA) pairings. For all studies, saline or ethanol (1.0, 1.5,2.0 g/kg i.p.) was administered 15 min before training, and saline or varenicline (0.05, 0.1, 0.2 mg/kg i.p.) was administered 60 min before either training or testing. For blood alcohol analysis, saline or varenicline (0.1 mg/kg) was administered 60 min before collection, and saline or ethanol (1.0, 1.5, 2.0 g/kg) was administered 15 min before collection. Varenicline dose-dependently ameliorated ethanol-induced conditioning deficits for all three doses of ethanol when administered before training but not when administered 24 h later, before testing. In addition, varenicline did not alter blood alcohol concentration. The smoking cessation aid varenicline may have therapeutic uses for treating ethanol-associated disruptions in cognitive processes. (C) 2008 Elsevier Inc. All rights reserved.