A small study at Aarhus University suggests the weight‑loss drug semaglutide can alter reward‑seeking behaviour and brain activity in healthy mice. The researchers report that daily doses changed how animals pursued natural rewards and how they responded to stress, accompanied by shifts in brain rhythms within a key reward circuit. The work is published in Molecular Brain.
Semaglutide is widely used to treat diabetes and obesity and is known by brand names such as Ozempic and Wegovy. It works by mimicking the hormone GLP‑1, which helps regulate appetite and blood sugar, and researchers have begun exploring whether it could dampen cravings related to addiction.
Preserving a baseline nervous system in non‑obese, non‑diabetic animals, the team studied the nucleus accumbens, a brain region central to motivation, pleasure and reward. The study was led by Alejo Mosqueira and Sanaz Ansarifar, with colleagues including Sadegh Nabavi and Andrea Moreno.
In a two‑arm design, adult male mice were allocated to receive either weekly injections for eight weeks, mirroring human regimens, or daily injections to reflect the faster metabolism of mice and to track short‑term behavioural changes.
After the injection phase, the mice underwent a battery of tests measuring movement, anxiety and reward‑seeking, while researchers monitored food and water intake and body weight to gauge general health.
Both dosing schedules produced weight loss and reductions in eating and drinking, with statistical analyses indicating that the weight loss itself did not account for the observed behavioural changes.
Only the daily‑dosed group showed notable behavioural shifts. In an open‑field test, these mice jumped more against the walls, interpreted as an increased attempt to escape the arena.
A separate marble burying test did not yield statistically significant differences between treated and control animals.
In the nestlet shredding test, daily semaglutide reduced the amount of material shredded, suggesting changes in environmental exploration or a potential rise in anxiety.
To assess non‑food rewards, researchers used a scent test in which healthy male mice typically seek the odour of female urine. The semaglutide‑treated mice spent far less time sniffing the female urine, indicating a dampened natural reward‑seeking drive.
On the forced swimming test, daily‑treated mice spent less time floating and more time actively swimming, a result commonly interpreted as improved stress resilience or an antidepressant‑like effect.
In a separate experiment, the team examined neural activity after a single semaglutide dose by anaesthetising mice and inserting electrodes into the nucleus accumbens to record local field potentials before, during and after injection.
Following administration, the dominant rhythms in delta, theta and alpha bands became slightly faster, while their amplitudes fell, a pattern the researchers say aligns with dampened reward anticipation.
Researchers caution the findings come from a small group of animals and that the brain recordings were made under anaesthesia, which alters neural activity and precludes direct linking to behaviour observed in awake animals.
Further work is needed to track brain activity in awake, freely moving mice and to explore different dosing schedules, to determine whether these effects generalise to other regimens.
Authors Alejo Mosqueira, Sanaz Ansarifar, Sadegh Nabavi and Andrea Moreno are credited on the study, which is titled Semaglutide alters behaviour and nucleus accumbens oscillatory activity in healthy mice.
