Semaglutide alters behavior and nucleus accumbens oscillatory activity in healthy mice

Glucagon-like peptide-1 (GLP-1) receptor agonists, like semaglutide, are well-established treatments for type 2 diabetes and obesity, primarily recognized for their metabolic benefits. However, growing evidence suggests these compounds exert significant central effects, particularly on reward pathways in the brain, which are relevant to conditions like addiction. While preclinical studies have indicated that GLP-1 agonists can modulate stimulant-related dopamine signaling and drug-seeking behaviors, the precise impact of semaglutide on the brain and behavior in otherwise healthy, non-diseased subjects remains largely unexplored. Understanding these baseline effects is critical for fully interpreting its broader therapeutic potential and mechanisms.

Researchers administered semaglutide 0.1 mg/kg daily to healthy mice to investigate its effects on behavior. The study employed various behavioral tests designed to assess aspects related to stress and reward pursuit over a period of daily dosing. Additionally, acute administration of semaglutide was used to examine its immediate impact on neural dynamics. The primary endpoint for this acute phase involved measuring changes in oscillatory activity within the nucleus accumbens, a key brain region involved in reward and motivation, across different frequency bands (delta, theta, alpha) using electrophysiological techniques.

Daily administration of semaglutide significantly altered behavior in healthy mice across various tests. These behavioral modifications were observed in paradigms designed to probe both stress responses and reward-seeking behaviors, indicating a broad impact on motivational and emotional processing. Furthermore, acute administration of semaglutide produced immediate and distinct changes in neural dynamics within the nucleus accumbens. Specifically, the oscillatory activity in this critical brain region was found to be altered across multiple frequency bands. The delta, theta, and alpha bands all exhibited modified patterns following semaglutide exposure. These findings collectively demonstrate that semaglutide directly influences both observable behaviors and underlying neural circuit activity in non-diseased brains.

Semaglutide impacts both behavior and neural dynamics in non-diseased brains, offering a crucial baseline for interpreting its broader therapeutic potential.