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Published on: July 25, 2017
Prucalopride, a serotonin type 4 receptor agonist, induces fast anxiolytic/antidepressant effects and concomitant
Sofia Cussotto1, Salma R Abdennebi1, Isabelle Etting2,3
1Université Paris-Saclay, UVSQ, Centre de recherche en Epidémiologie et Santé des Populations (CESP), UMR 1018, CESP-Inserm, Team Moods, Faculté de Pharmacie, Bâtiment Henri Moissan, Orsay, France.
Abstract:
Major Depressive Disorder (MDD) affects around 20% of people globally and is often comorbid with anxiety. This study investigates prucalopride, a serotonin type 4 receptor (5-HT4R) agonist approved for constipation, as a fast-acting anxiolytic/antidepressant using a mouse model of stress, based on corticosterone (CORT) administration. Behavioral effects of prucalopride (0.5 and 1.5 mg/kg/day) were compared to fluoxetine, a common SSRI, over 7 (subchronic) and 28 (chronic) days. Prucalopride showed faster and more significant improvements in emotionality scores than fluoxetine, reversing CORT-induced behavioral changes within 7 days. Gut microbiota analysis revealed CORT-induced changes at the subchronic timepoint. While chronic prucalopride did not alter microbial alpha diversity, it significantly shifted microbial composition (beta-diversity). Notably, prucalopride restored levels of the genus Ruminococcus, which were depleted by CORT. Our findings highlight prucalopride's rapid anxiolytic and antidepressant-like effects and its impact on gut microbiota, supporting the potential of 5-HT4R-targeting molecules as therapeutic options for psychiatric disorders.
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