Incentive salience and the neuropsychological underpinnings of cue-induced smoking relapse
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Principal Investigator: Francesco Versace Organization: UNIVERSITY OF TX MD ANDERSON CAN CTR Fiscal Year: 2024 Award: $359,579 Funding agency: National Institute on Drug Abuse PROJECT SUMMARY 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. Terms: <Affect><Affective><Animal Model><Animal Models and Related Studies><Behavior><Behavior Control><Behavioral><Behavioral Manipulation><Brain><Brain Nervous System><Categories><Cigarette><Classification><Common Rat Strains><Compulsive Behavior><Cue-induced relapse><Cues><Data><Development><Disease><Disorder><Eating><Eating Behavior><Encephalon><Event-Related Potentials><Food><Food Intake><Fostering><Funding><General Population><General Public><Goals><Grant><Hour><Human><Hyperphagia><Impulse Control Disorders><Incentives><Individual><Individual Differences><Intervention><Intervention Strategies><Knowledge><Laboratories><Lead><Mission><Modeling><Modern Man><Motivation><NIDA><National Institute of Drug Abuse><National Institute on Drug Abuse><Neurobiology><Neuropsychologies><Neuropsychology><Neurosciences><Nicotine><Nicotine Withdrawal><Obesity><Overeating><Participant><Pb element><Process><Property><Public Health><Rat><Rats Mammals><Rattus><Relapse><Research><Rewards><Risk><Smoker><Smoking><Smoking Behavior><Stimulus><Strategic Planning><Substance abuse problem><Systematics><Testing><Therapeutic Intervention><Translating><Translational Research><Translational Science><Translations><United States><Vulnerable Populations><abuse of substances><addiction><addictive disorder><adiposity><behavioral control><cognitive neuroscience><corpulence><craving><deprivation><developmental><drug seeking behavior><event related potential><habituation><heavy metal Pb><heavy metal lead><improved><incentive salience><individual response><individualized prevention><individualized response><innovate><innovation><innovative><intervention therapy><interventional strategy><model of animal><motivated behavior><neural><neurobehavioral><neurobiological><neurobiological mechanism><neurophysiological><neurophysiology><neuropsychologic><non-smoker><nonsmoker><personalization of treatment><personalized medicine><personalized prevention><personalized therapy><personalized treatment><polyphagia><pre-clinical><precision prevention><preclinical><prevent><prevent relapse><preventing><relapse prevention><response><smoking relapse><substance abuse><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><theories><trait><translation><translation research><translational investigation><vulnerable group><vulnerable individual><vulnerable people>