Varenicline ameliorates nicotine withdrawal-induced learning deficits in C57BL/6 mice.
Varenicline, a partial agonist for a4ss2 nicotinic acetylcholine receptors (nAChRs) and full agonist for a7 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.
Raybuck
Jonathan D
JD
Center for Substance Abuse Research, Temple University, Philadelphia, PA 19122, USA.
Portugal
George S
GS
Lerman
Caryn
C
Gould
Thomas J
TJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000627:therapeutic use*; D003213:Conditioning, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D007859:Learning Disabilities / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D011810:Quinoxalines / Q000627:therapeutic use*; D014029:Tobacco Use Disorder / Q000150:complications*; D000068580:Varenicline
D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D000068580:Varenicline