Our aim in the first study is to investigate the effect of two periods of nicotine deprivation, 6-hr and 18-hr, on smoking lapse behavior compared with 1 hr of deprivation which corresponds to the typical inter-cigarette interval for a pack-a-day smoker. The 6-hr nicotine deprivation condition represented acute deprivation, targeting increases in tobacco Brefeldin A order craving (Drobes & Tiffany, 1997), whereas the 18-hr deprivation condition represented a period of more prolonged deprivation, designed to target increases in craving as well as additional tobacco withdrawal symptoms (Hatsukami et al., 1984). Our goal in the first study was to identify the level of monetary reinforcement needed for each level of nicotine deprivation so that smokers, on average, delayed smoking for approximately half of the delay window (i.

e., ~25 min of the 50 min window). In subsequent investigations, this ��target model behavior�� will limit potential floor or ceiling effects when examining whether a medication increases or decreases the ability to resist smoking. The second study was designed to validate the smoking lapse model by examining medications with proven efficacy for counteracting effects of nicotine deprivation and increasing rates of smoking cessation. To this end, we examined whether varenicline and bupropion (Gonzales et al., 2006; Jorenby et al., 2006) increased the ability to resist smoking and reduced subsequent smoking. Importantly, we also examined the sensitivity of our model across factors which might impact on its ability to detect medication effects, including gender, income, motivation to quit, and nicotine dependence.

Medication development for alcohol use often examines GSK-3 drinkers who are at the heavier end of the dependence spectrum (Litten et al., 2012). Using a similar approach, we examined a subset of our sample that reported smoking within 5 min of waking. Smoking within the first 5 min of waking is fairly prevalent in smokers (~20%; Fagan et al., 2010; Fu et al., 2011; Luo et al., 2008), is found in higher rates in treatment seeking populations (Baker et al., 2007; Steinberg et al., 2011), and is associated with a pattern of heavy, uninterrupted, and automatic smoking (i.e., relatively insensitive to introceptive or exteroceptive cues) which is strongly predictive of poorer treatment outcomes, including shorter latency to lapse and relapse and faster progression from a lapse to relapse (Baker et al., 2007; Borland, Yong, O��Connor, Hyland, & Thompson, 2010; Fidler, Shahab, & West, 2011).