title: Developing and validating a human laboratory model to screen medications for smoking cessation.
abstract: BACKGROUND
  To facilitate translational work in medications development for smoking cessation, we have developed a human laboratory analogue of smoking lapse behavior. Our paradigm models 2 critical features of smoking lapse: the ability to resist the first cigarette and subsequent ad libitum smoking. In this paper we present the results of 2 studies designed to develop and validate the effect of nicotine deprivation on smoking lapse behavior.
  
  
  METHODS
  Study 1 (n = 30) was designed to develop the model parameters by examining varying levels of nicotine deprivation (1, 6, and 18 hr; within-subject) and identifying optimum levels of monetary reinforcement to provide while modeling the ability to resist smoking. Study 2 was designed to validate the model by screening smoking cessation medications with known clinical efficacy. Subjects (n = 62) were randomized to either varenicline 2 mg/day, bupropion 300 mg/day, or placebo, and we then modeled their ability to resist smoking and subsequent ad libitum smoking.
  
  
  RESULTS
  In Study 1, increasing levels of nicotine deprivation and decreasing levels of monetary reinforcement decreased the ability to resist smoking. In Study 2, the lapse model was found to be sensitive to medication effects among smokers who demonstrated a pattern of heavy, uninterrupted, and automated smoking (i.e., smoked within 5 min of waking). Ratings of craving, mood, withdrawal, and subjective cigarette effects are presented as secondary outcomes with results mirroring clinical findings.
  
  
  CONCLUSIONS
  Our smoking lapse model demonstrates promise as a translational tool to screen novel smoking cessation medications. Next steps in this line of research will focus on evaluating predictive validity.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, 2 Church Street South, Suite 109, New Haven, CT 06519, USA. sherry.mckee@yale.edu
authors.forename: Sherry A
authors.initials: SA
authors.lastname: McKee
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Weinberger
authors.forename: Julia
authors.initials: J
authors.lastname: Shi
authors.forename: Jeanette
authors.initials: J
authors.lastname: Tetrault
authors.forename: Sabrina
authors.initials: S
authors.lastname: Coppola
mesh_terms: D000293:Adolescent; D000328:Adult; D000339:Affect; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012646:Self Administration; D012907:Smoking; D016540:Smoking Cessation / Q000379:methods*; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control; D061485:Tobacco Use Cessation Devices; D016896:Treatment Outcome; D055815:Young Adult