title: Nicotinic receptor partial agonists modulate alcohol deprivation effect in C57BL/6J mice.
abstract: Relapse is a core feature of alcohol addiction and hinders the pharmacotherapy of alcohol use disorders. Pre-clinical and clinical studies have shown that neuronal nicotinic acetylcholine receptor (nAChR) partial agonists such as cytisine and its derivative, varenicline, reduce alcohol (ethanol) consumption and seeking behavior. However, the effects of these ligands on ethanol relapse are little understood. In the present study, we examined the effects of varenicline and cytisine on alcohol deprivation effect (ADE)--a validated model for relapse-like ethanol drinking in C57BL/6J mice. After habituation to 15% (v/v) ethanol intake using a continuous free-choice procedure, mice were exposed to alternating cycles of ethanol deprivation (5 days) and re-exposure (2 days). At the end of third deprivation cycle, animals received repeated intraperitoneal injections of saline, varenicline (0.5 or 3.0 mg/kg) or cytisine (0.5 or 3.0 mg/kg) and fluid intake was measured post 4 h and 24 h ethanol re-exposure. Repeated ethanol deprivation and re-exposure cycles significantly produced a robust and transient increase in ethanol (ADE). Pretreatment with varenicline (0.5 or 3.0 mg/kg) or cytisine (0.5 or 3.0 mg/kg) significantly reduced the expression of ADE at 4 h and 24 h after ethanol re-exposure. The results from this study indicate that nAChR partial agonists reduce the expression of ADE in mice and further suggest the involvement of nAChR mechanisms in ADE, a relapse-like ethanol drinking behavior.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Sajja
authors.forename: Shafiqur
authors.initials: S
authors.lastname: Rahman
mesh_terms: D000428:Alcohol Drinking; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001392:Azocines / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011807:Quinolizines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D000068580:Varenicline; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D001392:Azocines; D001552:Benzazepines; D018722:Nicotinic Agonists; D011807:Quinolizines; D011810:Quinoxalines; D000068580:Varenicline; C004712:cytisine; D000093843:Quinolizidine Alkaloids
keywords: Alcohol; Alcohol deprivation effect; Mice; Nicotinic receptor; Relapse; Varenicline