2026-06-04T12:43:41Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/333892026-02-03T11:26:35Zcom_10630_2254col_10630_37953

Arrabal-Gómez, Carlos Serrano-Castro, Pedro Sánchez-Pérez, José Andrés Garcia-Casares, Natalia Fuxe, Kjell Borroto Escuela, Dasiel Óscar Narváez, Manuel 2024-09-26T09:12:17Z 2024-09-26T09:12:17Z 2024-04-18 Carlos Arrabal-Gómez, Pedro Serrano-Castro, Jose Andrés Sánchez- Pérez, Natalia Garcia-Casares, Kjell Fuxe, Dasiel Borroto-Escuela & Manuel Narváez (2024) Potentiation of antidepressant effects: NPY1R agonist and ketamine synergy enhances TrkB signaling and neurogenesis in the ventral hippocampus, Expert Opinion on Therapeutic Targets, 28:4, 309-322, DOI: 10.1080/14728222.2024.2342524 https://hdl.handle.net/10630/33389 10.1080/14728222.2024.2342524 Background: Major Depressive Disorder (MDD) poses a significant challenge to global health, with current treatments often limited by efficacy and onset delays. This study explores the synergistic antidepressant-like effects of an NPY1R agonist and Ketamine, targeting their neurobiological interactions within the ventral hippocampus. Research Design and Methods: Utilizing a preclinical model, this study administered Neuropeptide Y receptor 1 (NPY1R) agonist and Ketamine, both separately and in combination, through intracerebroventricular (icv) and intranasal (i.n.) routes. The Forced Swimming Test (FST) was employed to assess antidepressant-like activity, while in situ Proximity Ligation Assay and immunohistochemistry were used to examine NPY1R/TrkB heteroreceptor complexes and BDNF expression in the ventral dentate gyrus (DG), along with neurogenesis markers. Results: The combined treatment significantly reduced immobility in the FST, indicative of enhanced antidepressant-like effects, correlated with increased formation of NPY1R/TrkB complex and brainderived neurotrophic factor (BDNF) expression in the ventral DG. These molecular alterations were associated with increased neurogenesis. Conclusions: The coadministration of an NPY1R agonist and Ketamine in a rodent model demonstrated potentiated antidepressant responses through synergistic neurobiological pathways, including TrkB signaling and hippocampal neurogenesis. This indicates a novel therapeutic strategy for MDD, warranting further clinical investigation to fully understand its implications. eng http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 Internacional Depresión - Tratamiento Potentiation of antidepressant effects: NPY1R agonist and ketamine synergy enhances TrkB signaling and neurogenesis in the ventral hippocampus journal article