# Dopaminergic control of obesity in mice

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $504,071

## Abstract

Abstract
Losing weight can be life saving for people with obesity. Although many people with obesity lose weight with
diet and exercise, the vast majority regain this lost weight over time. Multiple pharmacological treatments have
been approved by the US Food and Drug Administration (FDA) to help patients lose weight. However, in each
case the effect of these treatments is temporary, and weight is regained when the treatment is stopped. This
means that patients must take these medications for the rest of their lives to realize their health benefits. In
addition to the financial cost of life-long medication, patients must contend with side effects and medication
resistance. As such, there remains an unmet need for new medical interventions that produce weight loss
without lifelong treatment. In this proposal we aim to investigate how dopamine function is altered as animals
gain weight. Reductions in dopamine function have been linked to obesity, and drugs that decrease dopamine
function (such as antipsychotic medications) cause weight gain. This leads to our central hypothesis that
obesity reduces dopamine release in the nucleus accumbens (NAc), which causes overeating and
weight gain. A corollary of this hypothesis is that boosting dopamine release would lead to weight loss.
Indeed, either direct stimulation of dopamine neurons or administration of drugs that increase dopamine
release (such as amphetamine) cause weight loss. However, due to side effects and abuse liability,
dopaminergic stimulants are not useful therapeutics. For this reason, our primary Aim is to understand the
cellular changes in dopamine function that occur as animals become obese, to inform the design of
neuromodulation approaches to permanently reverse these changes to drive lasting weight loss without life-
long medication. To test this hypothesis, we propose to compare in vivo dopamine release in the nucleus
accumbens of control vs. obese mice (Aim 1). We will also employ ex vivo electrophysiological approaches to
determine the cellular mechanisms underlying changes in dopamine neuron activity in obese mice (Aim 2).
And finally, we will engage neuroplasticity in dopamine neurons to chronically boost dopamine release, to test
whether this causes long-lasting reductions in food intake and body weight (Aim 3). This research will provide a
critical foundation to advance efforts for modulating food seeking and intake, to inform and improve weight loss
outcomes in people with obesity.

## Key facts

- **NIH application ID:** 10912762
- **Project number:** 5R01DK136810-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Alexxai V Kravitz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $504,071
- **Award type:** 5
- **Project period:** 2023-08-25 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912762

## Citation

> US National Institutes of Health, RePORTER application 10912762, Dopaminergic control of obesity in mice (5R01DK136810-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10912762. Licensed CC0.

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