title: Passive immunization against nicotine attenuates somatic nicotine withdrawal syndrome in the rat.
abstract: BACKGROUND
  Nicotine immunization is under consideration as an intervention for smoking cessation. Therefore, it was of interest to evaluate the effects of nicotine antibodies on the withdrawal syndrome following termination of chronic nicotine administration.
  
  
  METHODS
  Experiment 1 determined whether passive immunization following continuous nicotine infusion would alter the intensity of nicotine withdrawal syndrome in the rat. Fourteen rats were rendered nicotine dependent by 7 days of subcutaneous nicotine bitartrate infusion. On the final day, seven rats received 150 mg intraperitoneal (i.p.) of immune gamma globulin (IgG) raised against 3'-aminomethylnicotine-recombinant Pseudomonas aeruginosa exoprotein A (NicVAX, Nabi Biopharmaceuticals, Rockville, MD) and seven rats received normal IgG. Rats were observed under blind conditions for somatically expressed nicotine abstinence signs immediately prior to drug termination and at 12, 24, and 36 hr afterward. In Experiment 2, similarly treated rats were observed at 6- and 72-hr postwithdrawal, to test the possibility that immunization altered the time course rather than the intensity of withdrawal syndrome. Experiment 3 tested whether immunized rats were still nicotine dependent. Without pump removal, each rat was challenged by 1/mg/kg mecamylamine HCl and observed for precipitated withdrawal syndrome.
  
  
  RESULTS
  In Experiment 1, there was no premature withdrawal syndrome during nicotine infusion. After termination, the immunized group had significantly fewer withdrawal signs than controls. Experiment 2 showed that immunization did not simply alter the timing of the nicotine abstinence syndrome since immunization did not increase signs before or after the usual withdrawal timeframe. In Experiment 3, rats immunized on the final day of infusion were still nicotine dependent since they exhibited a vigorous mecamylamine-precipitated withdrawal syndrome.
  
  
  CONCLUSIONS
  Nicotine antibodies did not precipitate a withdrawal syndrome, and they markedly reduced the severity of spontaneous nicotine withdrawal. The present data suggests that this may be most readily explained by their reported delay of nicotine clearance.
authors.affiliation: University of Houston-Clear Lake, 2700 Bay Area Blvd., Houston, TX 77058, USA. malin@uhcl.edu
authors.forename: David H
authors.initials: DH
authors.lastname: Malin
authors.forename: William D
authors.initials: WD
authors.lastname: Moon
authors.forename: Pilar
authors.initials: P
authors.lastname: Goyarzu
authors.forename: Nancy
authors.initials: N
authors.lastname: Magallanes
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Blair
authors.forename: Melodee R
authors.initials: MR
authors.lastname: Alexander
authors.forename: Lauren
authors.initials: L
authors.lastname: McDavid
authors.forename: Jason L
authors.initials: JL
authors.lastname: Spurgeon
authors.forename: Sofiane
authors.initials: S
authors.lastname: Ennifar
authors.forename: Ali
authors.initials: A
authors.lastname: Fattom
mesh_terms: D000818:Animals; D007116:Immunization, Passive / Q000379:methods*; D008297:Male; D009538:Nicotine / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000276:immunology; D014029:Tobacco Use Disorder / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D009538:Nicotine