title: Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.
abstract: Sex differences in the sensitivity to nicotine may influence vulnerability to tobacco dependence. The goal of this study was to investigate the dose-response function for the reinforcing and subjective effects of intravenous nicotine in male and female smokers. Tobacco-dependent subjects (12 male and 14 female) participated in four experimental sessions in which they received sample infusions of saline and nicotine (0.1, 0.2, 0.3, or 0.4 mg doses) in a randomized double-blind crossover design. During each session, subjects first received the sample infusions, and heart rate (HR), blood pressure, and subjective stimulatory, pleasurable and aversive responses were monitored. Immediately following the sample infusions, subjects self-administered either nicotine or saline in six double-blind forced-choice trials. A sex by dose interaction was observed in the nicotine choice paradigm. Nicotine self-administration rate was negatively correlated with nicotine dose in males (males displayed choice preference for low doses of nicotine over high doses of nicotine), but no significant relationship between dose and choice preference was evident in females. Relative to placebo, sample doses of nicotine increased heart rate and blood pressure, and induced stimulatory, pleasurable, and aversive subjective effects. Diastolic blood pressure increased dose dependently in males, but not in females. These findings, which demonstrate sex differences in nicotine self-administration for doses that are near to the reinforcement threshold, suggest that male and female smokers may respond differently to the changes in nicotine doses available for self-administration.
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University, VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Jensen
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University, VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: Elise E
authors.initials: EE
authors.lastname: DeVito
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University, VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Valentine
authors.affiliation: Department of Biostatistics, Yale University School of Public Health and School of Medicine, New Haven, CT, USA.
authors.forename: Ralitza
authors.initials: R
authors.lastname: Gueorguieva
authors.affiliation: Department of Psychiatry, School of Medicine, Yale University, VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Sofuoglu
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D002755:Choice Behavior / Q000187:drug effects*; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D012646:Self Administration; D012727:Sex Characteristics; D014029:Tobacco Use Disorder / Q000523:psychology*
chemical_list: D009538:Nicotine