# Neural activity-based candidate gene identification to link eating disorders and drug addiction

> **NIH NIH UG3** · MAYO CLINIC ROCHESTER · 2024 · $201,750

## Abstract

PROJECT SUMMARY
Binge-eating disorder (BED) and bulimia nervosa (BN) are potentially life-threatening eating disorders that
share behavioral and brain similarities, genetic risk factors and higher-than-expected comorbidities with drug
addiction – suggesting a common etiology. However, no mechanistic study has examined this possibility due in
part to the lack of an animal model linking eating disorders and drug addiction. Like drug craving and use in
drug addiction, food craving and eating in BED/BN persist despite adverse consequences (punishment). Our
pilot data from rats indicate that extensive cocaine and alcohol histories, known to trigger addiction-like brain
changes and punishment-resistant “compulsive” drug intake in rats, trigger punishment-resistant food intake or
“compulsive appetite”. These results provide an animal model for studying the neurobiological mechanisms
manifesting as compulsive behavior across eating disorders and drug addiction. Food motivation is thought to
be regulated by both homeostatic (caloric) and non-homeostatic (hedonic/incentive) systems. The homeostatic
system detects energy shortages and elicits food intake. However, like compulsive drug motivation, our data
suggest that compulsive appetite is driven by non-homeostatic “motivational/habitual” dysregulation. Like
cocaine and alcohol histories, obesogenic diet histories also led to compulsive appetite via non-homeostatic
dysregulation. Thus, drug/diet-induced changes in brain sites that control non-homeostatic regulation, such as
reward circuits, likely cause compulsive appetite. We previously found that appetitive behavior is, in part,
controlled by ‘food-reactive’ neurons (as indicated by the activation marker Fos) in the infralimbic cortex (IL) –
a part of reward circuits thought to regulate drug and food motivation independently of energy homeostasis;
these neurons thus appear to function as “accelerators” for non-homeostatic appetite regulation. We have also
found that extensive drug histories increase neural food-reactivities in IL and other brain sites within reward
circuits while inducing gene expression changes linked to aberrant neural plasticity and addiction preferentially
in food-reactive – rather than non-reactive – neurons. Such brain changes would entail more “acceleration” on
food motivation via non-homeostatic dysregulation, thereby likely manifesting as compulsive appetite. Based
on the rigor of previous research and premise above, this project will test the central hypothesis that extensive
cocaine/alcohol/obesogenic diet histories induce compulsive appetite via gene expression changes unique to
food-reactive neurons in the reward circuits. The reward circuits contain neurons selectively reactive to each
specific behaviorally relevant stimuli – likely exerting different behavioral functions. We will thus utilize neural
activity-specific gene expression profiling (Aim 1) and rescuing (Aim 2) to target food-reactive neurons. The
expected result...

## Key facts

- **NIH application ID:** 11122982
- **Project number:** 7UG3DA055167-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Nobuyoshi Suto
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $201,750
- **Award type:** 7
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11122982

## Citation

> US National Institutes of Health, RePORTER application 11122982, Neural activity-based candidate gene identification to link eating disorders and drug addiction (7UG3DA055167-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11122982. Licensed CC0.

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