title: Nicotine-induced locomotor sensitization: pharmacological analyses with candidate smoking cessation aids.
abstract: There are a number of approved therapeutics for the management of alcohol dependence, which might also convey the potential as smoking cessation aids. The present study investigated the effect of a few of these therapeutics and potential candidates (non-peptide vasopressin V1b antagonists) on the expression of nicotine-induced behavioral sensitization in Wistar rats. The following compounds were included in this evaluation: rimonabant, bupropion, topiramate, acamprosate, naltrexone, mecamylamine, nelivaptan (SSR-149415, V1b antagonist) and two novel V1b antagonists. Following the development of nicotine-induced locomotor sensitization and a withdrawal period, the expression of sensitization was assessed in the presence of one of the examined agents given 30 minutes prior to the nicotine challenge injection. Acamprosate, naltrexone, rimonabant, mecamylamine, nelivaptan and V1b antagonist 'compound 2' significantly antagonized the expression of nicotine-induced sensitization. Whereas topiramate showed a trend for effects, the V1b antagonist 'compound 1' did not show any significant effects. Bupropion failed to block sensitization but increased activity alone and was therefore tested in development and cross-sensitization studies. Taken together, these findings provide pre-clinical evidence that these molecules attenuated the expression of nicotine-induced sensitization and should be further investigated as putative treatments for nicotine addiction. Moreover, V1b antagonists should be further investigated as a potential novel smoking cessation aid.
authors.affiliation: Abbott Healthcare Products B.V., Weesp, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Goutier
authors.affiliation: Abbott Healthcare Products B.V., Weesp, The Netherlands.
authors.forename: Margreet
authors.initials: M
authors.lastname: Kloeze
authors.affiliation: Abbott Healthcare Products B.V., Weesp, The Netherlands.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: McCreary
mesh_terms: D000077443:Acamprosate; D000704:Analysis of Variance; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology; D016642:Bupropion / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009271:Naltrexone / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D017208:Rats, Wistar; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D061485:Tobacco Use Cessation Devices; D000077236:Topiramate
chemical_list: C456029:1-(5-chloro-1-((2,4-dimethoxyphenyl)sulfonyl)-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide; D065092:Antidiuretic Hormone Receptor Antagonists; D007211:Indoles; D018722:Nicotinic Agonists; D011759:Pyrrolidines; D016642:Bupropion; D000077236:Topiramate; D013654:Taurine; D005632:Fructose; D009271:Naltrexone; D009538:Nicotine; D000077443:Acamprosate
keywords: Cessation aids; nicotine behavioral sensitization; pharmacological strategies