Grace Sferrazza (CAS`26, COM`26)

Drugs like Wegovy, Ozempic, and Zepbound have taken the world by storm, helping millions shed pounds quickly. But as waistlines shrink, researchers are asking a deeper question: What are these drugs doing to our brains?

Assistant Professor of Biology Lynne Chantranupong is leading a research team to figure out the long-term neurological effects of GLP-1R agonists—the class of drugs behind these weight-loss miracles. Her lab is investigating how these medications could alter dopamine levels and reshape the brain’s reward system.

“It’s a blockbuster drug and millions of people are taking it,” Chantranupong says. “But it has all of these side effects on your behavior that we don’t understand.”

One of the lab’s researchers is Justin Arrick (CAS ’26), a biochemistry and molecular biology major who joined the team through BU’s Undergraduate Research Opportunities Program (UROP). Together, they’re studying how GLP-1R agonists affect long-term motivated behavior—actions driven by craving or desire.

GLP-1 agonists mimic a hormone called glucagon-like peptide-1, which lowers blood sugar and creates a feeling of fullness. While effective for weight loss, users have reported unexpected side effects like mood changes, reduced enjoyment in daily activities, and even a diminished desire for alcohol.

“[People] even lose their desire for alcohol, [so] that kind of all rang a bell,” Chantranupong says. “That likely involves dopamine, and how this drug may kind of impact that major neurotransmitter.”

Dopamine is the brain’s chemical messenger for pleasure and reward. It helps determine how satisfying an action feels—like eating a favorite snack or enjoying a drink. Chantranupong’s lab thinks that GLP-1R agonists may be rewiring the brain’s dopamine circuits, so people feel a lower sense of reward.

To test this theory, Chantranupong and Arrick are working with mice to understand how their behavior changes in response to the drug over a long period of time. Using a technique called fiber optometry, they’re tracking dopamine-related brain activity before and after administering the drug. The mice are offered sweet and less-sweet solutions after eating, mimicking how a human would reach for a sweet treat over a savory snack.

“There’s this protein that gets expressed in the brain anytime a neuron fires,” says Arrick. “You could use that to identify certain regions of the brain that are being affected, because you’ll see differences in that protein’s levels, which then you could visualize.”

Arrick’s duties include streamlining the analysis processes to highlight the mice’s dopamine levels while they complete a task. Arrick has also been “the driving force” of developing a computational workflow to analyze brain activity and pinpoint which regions are changing, Chantranupong says. Arrick joined the Chantranupong Lab as a student in the Undergraduate Research Opportunities Program (UROP) in January of 2024, shortly after Professor Chantranupong arrived at BU, and is now a BA/MA student.

The team is nearly finished mapping the brain slices—visual depictions of specific areas that light up during activity. They hope to identify the circuits responsible for motivation and determine how the drug alters them. This could help scientists understand—and potentially reverse—unwanted behavioral side effects.

Most existing studies on GLP-1 agonists are short-term, lasting only a few weeks. Chantranupong believes that’s not enough. Short term studies could capture the adverse effects and not the long term changes on how neurons are firing, she says. Given that users could be on this drug for years, it’s imperative to look at its lasting effects.

“When you take a drug, you want to know what it is doing to you, not just to your weight, but your behavior. And if that’s adverse, how do you undo that?” said Chantranupong. “We hope to use that information to then inform us of which are the important circuits, and to… tinker with them to determine what’s affecting this loss of drive and motivation.”