The primary aim of this R21 exploratory/developmental grant is to examine the role of negative affect on smoking lapse behavior in women and men using a novel laboratory self-administration paradigm. Although negative affect has been implicated as a primary mechanism involved in tobacco relapse episodes, few studies to date have examined smoking in response to negative affect cues and none have examined gender differences in these relationships. Increasing our understanding of affect-mediated smoking lapse behavior is important as the majority of abstinent smokers (up to 90%) who experience a lapse, return to baseline smoking levels. Using an adaptation of our alcohol self-administration model (O'Malley et al., 2002), we are proposing to develop a human laboratory model of ad-lib smoking to examine the influence of negative affect on two primary aspects of early lapse behavior: 1) ability to resist the first cigarette and 2) subsequent smoking. Using a within-subject design, daily smokers who are mildly nicotine deprived will receive an affect induction (negative or neutral), and then will have the option of initiating a tobacco self-administration session or delaying initiation by five-minute increments for up to 50 minutes in exchange for monetary reinforcement. Subsequently, the tobacco self-administration session entails a 1-hour period in which subjects can choose to smoke using a smoking topography system or receive monetary reinforcement for cigarettes not smoked. We are currently using this proposed model in a study investigating the effect of alcohol on smoking lapse behavior (P50-DA13334 -O 'Malley; Project PI-McKee). For the proposed study, we are planning to use similar procedures to our ongoing alcohol-smoking lapse study to facilitate cross-study comparisons. This will allow us to examine the relative influence of cues (alcohol versus negative affect) known to contribute to tobacco relapse to further validate the sensitivity of this novel self-administration paradigm to model smoking lapse behavior. Ultimately, it is hoped that this model could be extended to evaluate the effect of pharmacological agents on tobacco relapse behavior. [unreadable] [unreadable]