title: Effect of varenicline on the acute and repeated locomotor responses to nicotine in rats.
abstract: The objective of this study was to evaluate the efficacy of varenicline, a novel partial agonist at alpha 4 beta 2 and full agonist at alpha 7 nicotinic acetylcholine receptor (nAChR) subtypes, in blocking the locomotor effects of acute or repeated treatments with nicotine (0.4 mg/kg, s.c.) in rats. Varenicline (0.3-3 mg/kg, s.c.) by itself enhanced the basal locomotor activity in naive rats while it had an inhibitory effect on acute nicotine-induced hyperlocomotion. Varenicline (0.3-3 mg/kg) did not change the nicotine-evoked conditioned locomotion, but when administered to nicotine-sensitized rats (0.1 and 1 mg/kg), reduced the expression of nicotine sensitization. In another set of experiments, varenicline (1 mg/kg) administered during the second withdrawal period (days 11-14) to nicotine-treated rats, attenuated the reestablishment of the expression of nicotine sensitization. Our pharmacological analyses further support the hypothesis that varenicline might be a useful treatment for smoking cessation considering its actions on the locomotor and reinforcing effects of nicotine without inhibition of conditioned locomotion.
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zaniewska
authors.forename: Andrew C
authors.initials: AC
authors.lastname: McCreary
authors.forename: Roman
authors.initials: R
authors.lastname: Stefański
authors.forename: Edmund
authors.initials: E
authors.lastname: Przegaliński
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Filip
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D004334:Drug Administration Schedule; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology*; D000068580:Varenicline; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D001552:Benzazepines; C579165:Chrna7 protein, rat; D011810:Quinoxalines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D009538:Nicotine; D000068580:Varenicline