SAN DIEGO — New research is uncovering how medications targeting the glucagon-like peptide-1 (GLP-1) system affect brain circuits involved in nausea, thirst, and pleasurable behaviors. These findings will be presented at Neuroscience 2025, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.
Medications targeting the GLP-1 system are effective treatments for type 2 diabetes and obesity. GLP-1 drugs mimic a hormone that is naturally released in the gastrointestinal tract in response to eating and act in the brain to reduce hunger. However, these medications result in side effects like nausea and vomiting in up to 40% of people who take them, causing many patients to discontinue treatment. Researchers are investigating whether some of the adverse actions of GLP-1 drugs can be separated from their effects on weight loss, as well as potential other beneficial uses of these medications.
Today’s new findings show that:
- Combining low doses of the drug tirzepatide, a “dual agonist” that works, in part, by activating GLP-1 receptors, with the hormone oxytocin results in weight loss without gastrointestinal side effects in obese rats. (James E. Blevins, University of Washington)
- Nerve cells in the area postrema — the brain’s vomit center — are important for both weight loss and nausea in response to GLP-1 drugs in mice. (Warren Yacawych, University of Michigan)
- In mice, activation of GLP-1 receptors on cells in the central amygdala activates a newly identified brain circuit that suppresses signals driving pleasure-based eating. (Ali D. Güler, University of Virginia)
- GLP-1 receptor agonists suppress thirst as well as appetite, and a region in the forebrain of rats called the median preoptic area appears to be involved in this effect. (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.”
This research was supported by national funding agencies including the National Institutes of Health (NIH), Department of Veterans Affairs (VA), and private funding organizations. This content is the sole responsibility of the authors and does not necessarily reflect the views of NIH or VA. For complete access to Neuroscience 2025 in person and online, request media credentials.
Monday, November 17, 2025
9–10 a.m. PST
San Diego Convention Center, Room 15A, and online for registered media
GLP-1 Press Conference Summary
- GLP-1 medications effectively treat type 2 diabetes and obesity by curbing hunger, but these drugs often cause gastrointestinal side effects like nausea and vomiting, as well as decreases in other motivated behaviors like thirst.
- Working with rodent models, research demonstrates that GLP-1 drugs affect reward processing in the brain, and ongoing efforts are working to reduce the gastrointestinal side effects of these drugs.
The anti-obesity effect of tirzepatide is augmented by systemic oxytocin treatment in male diet-induced obese rats
James E. Blevins, jeblevin@uw.edu, Abstract PSTR033.02
- Tirzepatide (TZP; Mounjaro®) is dual GLP-1 receptor (GLP-1R)/glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist approved to treat obesity and type 2 diabetes, but can also cause side effects of nausea, vomiting, and loss of muscle mass. The hormone oxytocin can also reduce bodyweight and does not cause nausea or vomiting.
- Researchers treated obese rats with low doses of TZP combined with the hormone oxytocin and examined body weight and kaolin intake — a soft clay animals consume when nauseated — over 28 days.
- While oxytocin and low-dose TZP treatment each reduced body weight by 6-7% when given alone, the combined treatment resulted in nearly double the weight loss (11%). The rats showed reduced food intake and body fat mass without increased kaolin, suggesting they did not have gastrointestinal side effects.
- The results suggest that oxytocin treatment could be combined with lower-dose TZP to reduce body weight without adverse gastrointestinal side effects.
A single dorsal vagal complex circuit mediates the aversive and anorectic responses to GLP1R agonists
Warren Yacawych, yacawych@umich.edu, Abstract PSTR083.12
- GLP-1 receptor agonists curb hunger and cause weight loss through their actions in the brain. But they can also trigger nausea and vomiting, which causes many patients to stop taking the drugs.
- Researchers targeted GLP-1 receptor agonists to the nucleus tractus solitarius (NTS) — an area involved in satiety — and the area postrema — involved in vomiting — to understand if each of these areas respectively control weight loss and nausea during treatment.
- Even though NTS cells that contain GLP-1 receptors help to naturally control body weight, targeting GLP-1 receptor agonists to this area alone did not cause any weight loss.
- Targeting GLP-1 drugs to the area postrema — the brain’s vomit center — caused both weight loss and nausea.
- The results suggest the area postrema is key for both the weight loss and nausea responses to GLP-1 receptor agonists, and de-coupling nausea from appetite suppression will be a key challenge in improving GLP-1 therapies.
A brain reward circuit inhibited by next-generation weight loss drugs
Ali D. Güler, aguler@virginia.edu, Abstract PSTR151.06
- The GLP-1 receptor agonists can cause weight loss and appetite suppression, but the neural mechanisms of their effects are not fully understood.
- In studies of genetically engineered mice, researchers showed that GLP-1 drugs act on two distinct brain systems: one that regulates hunger and another that dampens cravings for highly “rewarding” foods.
- They examined a population of cells that express GLP-1 receptors in the central amygdala. When activated, the cells decrease food intake. These cells connect to the ventral tegmental area — an area important for dopamine signaling in response to “rewarding” stimuli.
- Activating the central amygdala neurons decreased dopamine output in this reward-related circuit, indicating that a circuit links the amygdala, brainstem, and midbrain and is important in pleasure-based eating. They suggest that this pathway may be involved in binge eating, addiction, and other disorders rooted in reward circuits.
The impact of drinking on neural activity glucagon-like peptide-1 receptor immunoreactivity in vasopressin-deficient Brattleboro rats
Derek Daniels, danielsd@buffalo.edu, Abstract PSTR083.03
- GLP-1 receptor agonists decrease thirst as well as food intake. A specific strain of laboratory rats (Brattleboro rats) are hypersensitive to the thirst-specific effects of GLP-1 drugs.
- Investigations of the brains of Brattleboro rats suggest that several regions involved in the sensation of thirst — including the nucleus of the solitary tract and the median preoptic area — showed significant changes in GLP-1 receptor expression after thirsty animals were rehydrated.
- The findings shed light on how GLP-1 agonists produce thirst suppression and could provide guidance in developing drugs that avoid thirst-related side effects.
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