title: SU-6656, a selective Src kinase inhibitor, attenuates mecamylamine-precipitated nicotine withdrawal syndrome in mice.
abstract: BACKGROUND
  Src kinase is reported to regulate neuronal nicotinic acetylcholine receptor activity, which is among the principal receptor systems acted upon by nicotine. Src kinase is documented to mediate the pathogenesis of substance dependence. Therefore, the present study has been designed to investigate the effect of SU-6656, selective src kinase inhibitor, on the development of nicotine dependence in a mouse model of mecamylamine-induced nicotine withdrawal syndrome.
  
  
  METHODS
  Our experimental protocol consisted of administration of nicotine (2.5 mg/kg, subcutaneously), 4 times daily for 7 days. In order to precipitate nicotine withdrawal, mice were given 1 injection of mecamylamine (3 mg/kg, intraperitoneally), 1 hr 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. Withdrawal syndrome was quantitated in terms of a composite withdrawal severity score (WSS), and withdrawal syndrome-related anxiety was assessed by elevated plus maze test results.
  
  
  RESULTS
  SU-6656 markedly and dose dependently (p < .01) attenuated mecamylamine-induced experimental nicotine withdrawal syndrome in mice measured in terms of WSS and anxiety score.
  
  
  CONCLUSIONS
  Thus, it is suggested that src kinase is involved in the development of nicotine dependence-induced precipitation of its withdrawal syndrome and thus may serve as a viable pharmacological target to tackle the problem of nicotine addiction.
authors.affiliation: Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Patiala, Punjab, India.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Rehni
authors.forename: Thakur Gurjeet
authors.initials: TG
authors.lastname: Singh
authors.forename: Sandeep
authors.initials: S
authors.lastname: Arora
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014029:Tobacco Use Disorder / Q000188:drug therapy; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007211:Indoles; D009292:Narcotic Antagonists; C416927:SU 6656; D013449:Sulfonamides; D008464:Mecamylamine; D009538:Nicotine; D019061:src-Family Kinases