GLP-1 receptor agonist semaglutide reduces appetite while increasing dopamine reward signaling

In male mice that are food-restricted, low doses of semaglutide reduce normal food intake but do not change their motivation to seek sugar or alter dopamine activity in a brain region linked to reward processing.

In male mice that are food-restricted, a single injection of semaglutide reduces behaviors related to seeking sugary rewards while increasing activity in dopamine-producing brain cells during consumption of those rewards.

In male mice that are food-restricted, semaglutide increases activity in brain cells involved in reward when they consume sugar, but not when they encounter a signal that predicts sugar will be coming. This suggests the drug affects how the brain responds to actual consumption, not to the expectation of it.

In male mice on a restricted diet, semaglutide increases dopamine activity when they encounter rewards, whether or not they stop seeking those rewards. This suggests the dopamine change occurs independently of the change in motivation.

Medications that activate GLP-1 receptors are associated with lower urges to eat high-calorie foods and reduced persistent thoughts about food in people.

In male mice that are food-restricted, a low dose of semaglutide decreases normal food intake, but higher doses are needed to reduce interest in sugary rewards and change brain dopamine signals, suggesting these two types of feeding behavior respond differently to the drug.