title: Pharmacological modulation of farnesyltransferase subtype I attenuates mecamylamine-precipitated nicotine withdrawal syndrome in mice.
abstract: This study was designed to investigate the effect of FTI-276 trifluoroacetate, a selective inhibitor of subtype I, on the development of the mecamylamine-induced nicotine withdrawal syndrome. Mice were administered nicotine (2.5 mg/kg, subcutaneously) four times daily for 7 days. To precipitate nicotine withdrawal, mice were administered one injection of mecamylamine (3 mg/kg, intraperitoneally) 1 h after the last nicotine injection on the test day (day 8). Behavioral observations were made for a period of 30 min immediately after mecamylamine treatment. FTI-276 trifluoroacetate treatment markedly and dose-dependently attenuated the precipitated nicotine withdrawal syndrome, measured by a composite withdrawal severity score, jumping frequency, hyperalgesia in the tail flick test, and anxiety-like behavior in the elevated plus maze test. The results suggest that FTI-276 trifluoroacetate can inhibit the development of a precipitated nicotine withdrawal syndrome, and thus that farnesyltransferase subtype I may be a viable pharmacological target to tackle the problem of nicotine addiction.
authors.affiliation: Chitkara College of Pharmacy, Chitkara University, Chandigarh, Punjab, India.
authors.forename: Thakur G
authors.initials: TG
authors.lastname: Singh
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Rehni
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Arora
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D008297:Male; D008464:Mecamylamine / Q000009:adverse effects*; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D009538:Nicotine / Q000037:antagonists & inhibitors*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000009:adverse effects; D013375:Substance Withdrawal Syndrome / Q000201:enzymology* / Q000503:physiopathology / Q000523:psychology
chemical_list: D004791:Enzyme Inhibitors; C404062:FTI 276; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine; D008715:Methionine; D051231:Farnesyltranstransferase