Damiah Moore
Research Mentor: Shelly Flagel
Mentor Department: Psychiatry/MBNI, Medicine
Author(s): Damiah Moore, Daniela Pereira, Jenna McCloskey, Jacklyn Staffeld, Christopher Turner, Stephen Chang, Shelly Flagel
Session: Session 4 (1:00 PM – 1:50 PM)
Presentation Type: Poster 97
Abstract
Obesity is a major public health concern in the United States and Ozempic is emerging as a frontline treatment. The active component of Ozempic, semaglutide (SEMA), is a glucagon-like peptide-1 receptor agonist (GLP-1RA) used to treat obesity. GLP-1RAs regulate weight loss through actions on appetite, the induction of malaise/nausea, and modulation of reward processing. Anecdotal evidence supports the role of GLP-1RAs in reward processing, as people on these medications report reduced addiction-related behaviors like drug intake, compulsive shopping, and gambling. Clinical and preclinical evidence show that GLP-1RAs modulate reactivity to food- and drug-associated cues, suggesting the importance of cues in GLP-1RAs’ effects on motivated behavior. A mechanism underlying motivated behavior for food/drug rewards and associated cues is the attribution of incentive salience. This psychological process is regulated by mesolimbic dopamine and enhances “wanting” for rewards and reward-cues, but the role of SEMA in this process is unclear. Here, we examined whether acute GLP-1RA treatment alters attribution of incentive value to a food-associated cue and the motivation to work for food and food-cues. We tested this using adult male and female Sprague Dawley rats with Pavlovian conditioned approach (PavCA), conditioned reinforcement (CRT), and progressive ratio (PR) tests. PavCA was used to study individual differences in the attribution of incentive value to reward-cues, whereas CRT and PR were used to measure the motivation to work for the cue and food reward, respectively. Rats received a single saline or SEMA injection prior to behavioral tests. We measured kaolin intake, an indicator of malaise, to determine how sickness contributes to motivation effects. We found that acute SEMA treatment reduced incentive motivation for food-cues and the motivation to work for food and food-cues. Altogether, these data indicate that acute semaglutide blunts motivation for food and associated cues but may be driven by malaise.
