title: Effects of Nicotine Metabolites on Nicotine Withdrawal Behaviors in Mice.
abstract: BACKGROUND
  Rodent studies suggest that nicotine metabolites and minor tobacco alkaloids such as nornicotine and cotinine may promote cigarette smoking by enhancing nicotine rewarding and reinforcing effects. However, there is little information on the effects of these minor tobacco alkaloids on nicotine withdrawal. The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine and cotinine exhibit nicotine-like behavioral effects in a mouse model of spontaneous nicotine withdrawal.
  
  
  METHODS
  Mice were infused with nicotine or saline for 14 days. Experiments were conducted on day 15, 18-24 hours after minipump removal. Ten minutes prior to testing, nicotine-dependent ICR male mice received an acute injection of nicotine (0.05 and 0.5 mg/kg), nornicotine (2.5 and 25 mg/kg), or cotinine (5 and 50 mg/kg) to determine effects on somatic signs, anxiety-like behaviors, and hyperalgesia spontaneous signs of withdrawal.
  
  
  RESULTS
  Nicotine and the minor tobacco alkaloid nornicotine, but not cotinine, produced dose-dependent reversal of nicotine withdrawal signs in the mouse.
  
  
  CONCLUSIONS
  The minor tobacco alkaloid and nicotine metabolite nornicotine at high doses have nicotinic like effects that may contribute to tobacco consumption and dependence.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA.
authors.forename: Sagi
authors.initials: S
authors.lastname: Elhassan
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA.|Experimental Animals Breeding and Research Center, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Bagdas
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA.
authors.forename: M Imad
authors.initials: MI
authors.lastname: Damaj
mesh_terms: D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects; D003367:Cotinine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009538:Nicotine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome; D014029:Tobacco Use Disorder
chemical_list: D009538:Nicotine; D003367:Cotinine