Progress in basic neuroscience has improved our understanding of addiction neurobiology, but what has proven difficult is translating this knowledge into effective relapse prevention treatments. Identifying the neurobiological mechanisms underlying relapse will likely promote the development of better targeted therapeutic interventions to prevent it. In our previous funding cycle, we showed that smokers with larger brain responses to cigarette- related cues than pleasant stimuli are more vulnerable to relapse than smokers with the opposite brain reactivity profile. The objective of this renewal is to identify the neuropsychological mechanisms underlying these brain reactivity profiles and determine how these mechanisms affect vulnerability to cue-induced smoking relapse. Our central hypothesis is that the brain reactivity profiles that we isolated in smokers reflect individual differences in the tendency to attribute incentive salience to cues predicting rewards, a trait that increases vulnerability to cue- induced behaviors. Our hypothesis is based on the incentive sensitization theory and it is supported by preclinical findings and our own preliminary data. Animal models show that rats prone to attributing incentive salience to discrete food-related cues (called ?sign-trackers?) are more vulnerable to cue-induced drug seeking behavior than rats not prone to do so (called ?goal-trackers?). Our preliminary data show that the same neuropsychological trait predicts smoking relapse in smokers and cue-induced eating in the general population. We plan to test our hypothesis by pursuing two specific aims: 1) Identify the neuropsychological underpinnings of cue-induced behaviors. We will use the neurophysiological profiles derived from our newly developed cued food delivery task to classify 100 smokers and 100 nonsmokers as sign-trackers or goal-trackers, and predict cue-induced smoking and eating behaviors in the two groups. Our working hypotheses are that a) sign-trackers (both smokers and nonsmokers) will be more prone than goal-trackers to cue-induced eating and b) smokers categorized as sign-trackers in the cued food delivery task will be more prone than goal-trackers to cue-induced smoking in a laboratory model of smoking lapse behavior. 2) Determine the effects of nicotine withdrawal on cue-induced neurobehavioral responses. All participants will undergo two laboratory sessions. At session 2, smokers will be nicotine deprived for 24 hours. We hypothesize that nicotine deprivation will increase cue-induced smoking and eating behaviors in sign-trackers but not in goal-trackers. Our innovative neurobehavioral approach will advance bi-directional translation by allowing us to tie individual neurophysiological profiles to cue-induced be- haviors in humans. This project is significant because it will fundamentally advance our understanding of the mechanisms underlying impulse control disorders, the first step toward identifying new targets for personalized prevention and treatment interventions.
The proposed research is relevant to public health because it will allow us to identify the brain processes that lead some smokers to lose behavioral control and start compulsive smoking in the presence of cigarette-related cues. Identifying the neural underpinnings of cue-induced compulsive behaviors is likely to foster the development of new treatments targeting the brain processes responsible for cue-induced cravings and cue- induced relapses. Hence, this project is relevant to the NIDA Behavioral and Cognitive Neuroscience Branch mission of identifying individual differences that are associated with increased risk for addiction and predict individual responses to interventions.
| Cinciripini, Paul M; Green, Charles E; Robinson, Jason D et al. (2017) Benefits of varenicline vs. bupropion for smoking cessation: a Bayesian analysis of the interaction of reward sensitivity and treatment. Psychopharmacology (Berl) 234:1769-1779 |
| Versace, Francesco; Engelmann, Jeffrey M; Deweese, Menton M et al. (2017) Beyond Cue Reactivity: Non-Drug-Related Motivationally Relevant Stimuli Are Necessary to Understand Reactivity to Drug-Related Cues. Nicotine Tob Res 19:663-669 |
| Deweese, Menton M; Robinson, Jason D; Cinciripini, Paul M et al. (2016) Conditioned cortical reactivity to cues predicting cigarette-related or pleasant images. Int J Psychophysiol 101:59-68 |
| Versace, Francesco; Kypriotakis, George; Basen-Engquist, Karen et al. (2016) Heterogeneity in brain reactivity to pleasant and food cues: evidence of sign-tracking in humans. Soc Cogn Affect Neurosci 11:604-11 |
| Engelmann, Jeffrey M; Versace, Francesco; Gewirtz, Jonathan C et al. (2016) Individual differences in brain responses to cigarette-related cues and pleasant stimuli in young smokers. Drug Alcohol Depend 163:229-35 |
| Versace, F; Schembre, S M (2015) 'Obesogenic' oversimplification. Obes Rev 16:702-3 |
| Robinson, Jason D; Versace, Francesco; Engelmann, Jeffery M et al. (2015) The motivational salience of cigarette-related stimuli among former, never, and current smokers. Exp Clin Psychopharmacol 23:37-48 |
| Meyer, Mark J; Coull, Brent A; Versace, Francesco et al. (2015) Bayesian function-on-function regression for multilevel functional data. Biometrics 71:563-74 |
| Deweese, Menton M; Claiborne, Kimberly N; Ng, Jennifer et al. (2015) Dispensing apparatus for use in a cued food delivery task. MethodsX 2:446-57 |
| Versace, Francesco; Engelmann, Jeffrey M; Robinson, Jason D et al. (2014) Prequit fMRI responses to pleasant cues and cigarette-related cues predict smoking cessation outcome. Nicotine Tob Res 16:697-708 |
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