title: Varenicline ameliorates ethanol-induced deficits in learning in C57BL/6 mice.
abstract: Ethanol is a frequently abused drug that impairs cognitive processes such as learning. Varenicline, an alpha4beta2 nicotinic receptor partial agonist and alpha7 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; 30s, 85dB white noise)-foot shock unconditioned stimulus (US; 2s, 0.57mA) pairings. For all studies, saline or ethanol (1.0, 1.5, 2.0g/kg i.p.) was administered 15min before training, and saline or varenicline (0.05, 0.1, 0.2mg/kg i.p.) was administered 60min before either training or testing. For blood alcohol analysis, saline or varenicline (0.1mg/kg) was administered 60min before collection, and saline or ethanol (1.0, 1.5, 2.0g/kg) was administered 15min before collection. Varenicline dose-dependently ameliorated ethanol-induced conditioning deficits for all three doses of ethanol when administered before training but not when administered 24h 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.
authors.affiliation: Department of Psychology, Neuroscience Program, Temple University, Weiss Hall, Rm 865, 1701 N. 13th Street, Philadelphia, PA 19122, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Gulick
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Gould
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000437:Alcoholism / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011810:Quinoxalines / Q000494:pharmacology*; D016540:Smoking Cessation; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D002492:Central Nervous System Depressants; D011810:Quinoxalines; D000431:Ethanol; D000109:Acetylcholine; D000068580:Varenicline