In addition to reducing hunger, popular weight-loss drugs also affect reward processing and motivated behaviors.
New research is offering a clearer picture of how medications that target the glucagon-like peptide-1 (GLP-1) system influence brain networks involved in nausea, thirst, and reward-driven behaviors. These new results were recently shared at Neuroscience 2025, the annual meeting of the Society for Neuroscience and the world’s largest gathering for emerging discoveries in brain science and health.
Several well-known GLP-1 based medications, including Ozempic, Wegovy, and Mounjaro, were originally developed for type 2 diabetes but have also become widely used for weight management. These treatments imitate a natural hormone released in the gastrointestinal tract after eating, which then signals the brain to reduce appetite. Their effectiveness has made them popular among clinicians and patients.
However, GLP-1 medications are also associated with side effects such as nausea and vomiting, which occur in up to 40% of people who take them and often lead patients to stop treatment. Scientists are now working to better understand how these drugs influence the brain. One major focus is determining whether the unwanted reactions can be separated from the medications’ ability to support weight loss. Researchers are also exploring whether these drugs may have additional benefits beyond diabetes and obesity.
Key Findings From New Studies
Researchers report several new findings that deepen our understanding of how GLP-1–based medications influence the brain and body.
One study shows that combining low doses of tirzepatide — a dual GLP-1 and GIP receptor agonist — with the hormone oxytocin produces significant weight loss in obese rats without causing gastrointestinal side effects. While low-dose tirzepatide or oxytocin alone reduced body weight by 6–7%, the combined treatment nearly doubled the effect, producing an 11% reduction.
Treated rats also showed reduced food intake and fat mass without increases in kaolin consumption, a marker of nausea in animals. These results suggest that pairing oxytocin with lower-dose tirzepatide may offer a way to achieve weight loss while avoiding nausea and vomiting. (James E. Blevins, University of Washington)
The Brain’s Vomit Center and GLP-1 Drug Side Effects
Another study examined how different brain regions contribute to both weight loss and nausea caused by GLP-1 receptor agonists. Researchers targeted GLP-1 drugs to the nucleus tractus solitarius (NTS), which is involved in satiety signaling, and the area postrema, known as the brain’s “vomit center.” Although GLP-1 receptor–containing cells in the NTS normally help regulate body weight, delivering GLP-1 drugs directly to this region did not produce weight loss.
In contrast, activating GLP-1 receptors in the area postrema triggered both weight loss and nausea. These findings indicate that the area postrema plays a central role in mediating both desired and adverse effects of GLP-1 therapies, highlighting a major challenge in separating nausea from appetite suppression. (Warren Yacawych, University of Michigan)
A Newly Identified Reward Circuit Influenced by GLP-1 Drugs
A third study identified a previously unknown reward-related brain circuit influenced by GLP-1 receptor agonists. Using genetically engineered mice, researchers found that GLP-1 drugs act on two neural systems: one governing hunger and another moderating cravings for highly rewarding foods. They focused on a group of GLP-1 receptor–expressing cells in the central amygdala and discovered that activating these neurons reduced food intake.
These cells project to the ventral tegmental area, a central hub of dopamine signaling involved in processing rewarding stimuli. Stimulating the amygdala neurons reduced dopamine output in this circuit, suggesting the presence of a pathway linking the amygdala, brainstem, and midbrain that shapes pleasure-driven eating. This circuit may also contribute to binge eating, addiction, and other reward-related disorders. (Ali D. Güler, University of Virginia)
Understanding How GLP-1 Drugs Suppress Thirst
A final study explored how GLP-1 receptor agonists suppress thirst in addition to appetite. Researchers examined Brattleboro rats, a strain known for heightened sensitivity to the thirst-reducing effects of GLP-1 drugs. By analyzing the brains of animals before and after rehydration, the team found significant changes in GLP-1 receptor expression within regions associated with thirst regulation, including the nucleus of the solitary tract and the median preoptic area.
These insights shed light on the neural basis of GLP-1–induced thirst suppression and may help guide the development of future drugs that maintain appetite benefits while minimizing unwanted effects on hydration. (Derek Daniels, University at Buffalo)
“Research demonstrates an effect of these medications on the brain beyond treating diabetes and obesity, via mechanisms that are still not fully understood,” says Lorenzo Leggio, MD, PhD, a physician-scientist and clinical director of the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health. “GLP-1 therapies appear to have multiple synergistic effects that may be useful for treating chronic diseases with overlapping neural mechanisms, including binge eating disorders and addictive disorders.”
Meeting: Neuroscience 2025
This research was supported by national funding agencies including the National Institutes of Health (NIH), Department of Veterans Affairs (VA), and private funding organizations.
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