title: Targeting the noradrenergic system for gender-sensitive medication development for tobacco dependence.
abstract: BACKGROUND
  Tobacco use remains the leading cause of morbidity and mortality for both women and men in the United States, and women often experience poorer smoking cessation outcomes than men. Preliminary evidence suggests there are sex differences in medication effectiveness for smoking cessation. However, current medications do not take into account gender-sensitive treatment development and efficacy, underscoring the importance of this underdeveloped area of research.
  
  
  METHODS
  We reviewed preclinical and clinical evidence for gender differences in the inability to quit smoking by examining (a) the effect of increased negative affect and stress reactivity on smoking outcomes in women and (b) smoking for nicotine reinforcement in men. We also reviewed the current literature targeting the noradrenergic system as a novel gender-sensitive treatment strategy for tobacco dependence.
  
  
  RESULTS
  We hypothesize that noradrenergic agents that normalize noradrenergic activity may differentially attenuate stress reactivity in women and nicotine-related reinforcement in men, indicating that targeting the noradrenergic system for smoking cessation may be effective for both genders, with benefits operating through sex-specific mechanisms.
  
  
  CONCLUSIONS
  Converging lines of preclinical and clinical evidence suggest that gender-sensitive approaches to medication development for smoking cessation are a critical next step for addressing low quit rates and exacerbated health risks among women. Evidence reviewed indicates that smoking activates different brain systems modulated by noradrenergic activity in women versus men, and noradrenergic compounds may preferentially target these gender-sensitive systems.
authors.affiliation: Department of Psychiatry and Women's Health Research, Yale University School of Medicine, New Haven, CT;
authors.forename: Terril L
authors.initials: TL
authors.lastname: Verplaetse
authors.affiliation: Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY;
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Weinberger
authors.affiliation: Department of Psychiatry and Women's Health Research, Yale University School of Medicine, New Haven, CT;
authors.forename: Philip H
authors.initials: PH
authors.lastname: Smith
authors.affiliation: Department of Psychiatry and Women's Health Research, Yale University School of Medicine, New Haven, CT; Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT.
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Cosgrove
authors.affiliation: Department of Psychiatry and Women's Health Research, Yale University School of Medicine, New Haven, CT;
authors.forename: Yann S
authors.initials: YS
authors.lastname: Mineur
authors.affiliation: Department of Psychiatry and Women's Health Research, Yale University School of Medicine, New Haven, CT;
authors.forename: Marina R
authors.initials: MR
authors.lastname: Picciotto
authors.affiliation: Department of Psychiatry and Women's Health Research, Yale University School of Medicine, New Haven, CT;
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Mazure
authors.affiliation: Department of Psychiatry and Women's Health Research, Yale University School of Medicine, New Haven, CT; sherry.mckee@yale.edu.
authors.forename: Sherry A
authors.initials: SA
authors.lastname: McKee
mesh_terms: D005260:Female; D005783:Gender Identity; D006801:Humans; D008297:Male; D009538:Nicotine / Q000627:therapeutic use*; D011944:Receptors, Androgen; D016540:Smoking Cessation / Q000379:methods*; D000074606:Smoking Prevention; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
chemical_list: D011944:Receptors, Androgen; D009538:Nicotine