# Toward understanding dopamine receptor contributions to prediction error and reversal learning in anorexia nervosa

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $196,875

## Abstract

Project Summary/Abstract
Anorexia nervosa (AN) is an eating disorder associated with intense fear of weight gain, food refusal, and
severe weight loss. AN has the highest mortality rate among the psychiatric disorders; however, little is known
about biomarkers, and no medication has been approved for AN. Many individuals only partially recover, and
treatment options, especially for the psychological components of the illness, are not very effective, highlighting
the need for more effective treatments.
Brain reward pathways have a direct impact on the drive to eat, and a variety of neuroimaging studies have
suggested altered reward processing in AN. The neurotransmitter dopamine has a central role in the reward
circuitry to drive food approach, and the dynamic interplay between dopamine receptor response and food
restriction could have implications for the pathophysiology of AN. Dopamine-related brain function has been
studied indirectly using functional magnetic resonance brain imaging (fMRI) and tasks that deliver reward
stimuli unexpectedly, eliciting the so-called prediction error (PE) response. Research in AN showed repeatedly
altered PE processing suggesting altered dopamine circuit function in the disorder. Dopamine and PE
response have also been associated with altered reversal learning, which has important treatment implication
for AN as reversal learning is impaired in the disorder and modulation of the dopamine system could improve
treatment. However, the dopamine receptor mechanisms that underlie altered PE response in AN have not
been studied. This could be highly important to develop medication interventions.
 In this application, we will develop a study protocol and gather pilot data to identify whether specific
dopamine D2 challenge drugs can modulate PE response and reversal learning in AN. In Aim 1., we will apply
a selective dopamine D2 receptor agonist to test its effects on PE and reversal learning. In Aim 2., we will
apply a selective dopamine D2/3 receptor antagonist. We expect that those challenge drugs will lead to
opposite brain and behavior response within groups and directly support the involvement of those receptors in
PE and reversal learning processing. In Aim 3., we will contrast brain and behavior response across challenge
drugs in AN against response in healthy controls to gather pilot data for future investigation. This research will
be important to develop neurotransmitter specific pharmacological treatments for AN.

## Key facts

- **NIH application ID:** 9986913
- **Project number:** 5R21MH120475-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Guido KW Frank
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,875
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986913

## Citation

> US National Institutes of Health, RePORTER application 9986913, Toward understanding dopamine receptor contributions to prediction error and reversal learning in anorexia nervosa (5R21MH120475-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9986913. Licensed CC0.

---

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