# Regulation of Craving Under Stress: Neural Mechanisms and Novel Model

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $637,234

## Abstract

Abstract/Project Summary
Craving and the ability to regulate it are increasingly recognized for having key roles in the
maintenance of addictions (including nicotine dependence), and in the prevention of relapse. To
investigate these important processes, we developed the Regulation of Craving (ROC) task1-5. In this task,
nicotine-dependent smokers are exposed to smoking-related stimuli. In the craving condition, they are
instructed to think of the pleasant feelings associated with smoking, which results in cigarette craving. Then, in
the regulation condition, they are instructed to use a cognitive strategy to regulate their craving for cigarettes
(e.g., `think of the negative consequences associated with smoking')1. We used the ROC task and functional
magnetic resonance imaging (fMRI) to demonstrate that self-reported craving is significantly reduced during
the regulation condition, and that this depends on recruitment of regions in prefrontal cortex associated with
cognitive control, such as dorsolateral prefrontal cortex2, 6. We have also shown that recruitment of these brain
regions, in turn, modulates activity in subcortical regions that underlie craving, such as the ventral striatum2, 3, 7.
Stress is another key factor contributing to drug use in general and smoking in particular8. A leading
hypothesis is that stress contributes to smoking and relapse by potentiating craving and neural activity in brain
regions associated with craving (including ventral striatum)9-11. However, recent research suggests that stress
can also impair prefrontal function12. Thus, it is possible that stress may lead to drug use via two distinct
routes: by (1) potentiating craving and neural activity in craving-related regions (as shown with other
addictions), and also by (2) compromising the regulation of craving via decrements to prefrontal function.
To test our novel model and evaluate these alternative hypotheses, we will administer the ROC task to 84
nicotine-dependent smokers and 84 matched healthy controls in a 90-minute fMRI session. We will use threat
of electric shock, which is known to induce acute stress, on half the trials. We will compare (a) self-report and
(b) neural activity between craving and regulation conditions, in a 2x2x2 design: 2 ROC conditions (Craving vs.
Regulation) x 2 Stress conditions (Threat of Shock vs. Safe from Shock) x 2 Stimuli (Cigarettes vs. Appetitive
Food control). Exponential inter-trial intervals will ensure proper separation of neural events13, 14. To increase
clinical impact we will assess the contribution of each effect (Stress on Craving vs. Regulation) to
smoking severity. Finally, we will explore gender and individual differences in stress, craving, and the
regulation of craving, as they may moderate effects of stress, with implications for smoking cessation.
This project promises to advance our neurobiological understanding of stress, craving, and the
regulation of craving, as well as their interaction and contributi...

## Key facts

- **NIH application ID:** 10167660
- **Project number:** 5R01DA042911-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Hedy Kober
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $637,234
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167660

## Citation

> US National Institutes of Health, RePORTER application 10167660, Regulation of Craving Under Stress: Neural Mechanisms and Novel Model (5R01DA042911-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10167660. Licensed CC0.

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