# Incentive salience and the neuropsychological underpinnings of cue-induced smoking relapse

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $366,677

## Abstract

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 targ...

## Key facts

- **NIH application ID:** 9876542
- **Project number:** 2R01DA032581-05A1
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Francesco Versace
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $366,677
- **Award type:** 2
- **Project period:** 2012-07-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876542

## Citation

> US National Institutes of Health, RePORTER application 9876542, Incentive salience and the neuropsychological underpinnings of cue-induced smoking relapse (2R01DA032581-05A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9876542. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
