RT Journal Article
T1 A new pharmacological strategy against treatment-resistant depression
A1 Pineda-Gomez, Juan Pedro
A1 Millón-Peñuela, Carmelo
A1 Cantero García, Noelia
A1 Flores, Marta
A1 Ladrón de Guevara-Miranda, David
A1 Flores-Burgess, Antonio
A1 Díaz-Cabiale, Zaida
K1 Fisiología
K1 Depresión
K1 Farmacología
AB Major depressive disorder affects more than 50 million people in the world. However, 50% of patients don’trespond to two or more drugs or psychotherapeutic treatments, named treatment-resistant depression (TRD). Inthis work, we propose a new augmentation treatment against TRD based on combining Fluoxetine (FLX) and theN-terminal fragment Galanin, GAL(1–15). In Wistar Kyoto (WKY) rats, akin to endogenous depression genetically, we evaluate GAL(1–15)’s impact on FLX-induced behaviours on tests measuring despair and anhedonia.We explored GALR2 involvement using the antagonist M871 and an in vivo model with siRNA 5-HT1A knockdown. Also, the 5-HT1AR was analyzed by autoradiography binding in several brain regions. We analyze thecorticosterone levels and a dexamethasone-suppressed corticotropin-releasing hormone stimulation to study theHPA axis regulation. Our results shows that only the combination of FLX + GAL(1–15) induced antidepressanteffects in the WKY animals in Behavioural tests related to despair. This combination also reduced corticosteronelevels in the WKY animals and modulated the functional characteristics of the serotoninergic receptor 5-HT1A inthe prefrontal cortex. These novel results suggest combining GAL(1–15) with FLX is a new potentiation strategyin TRD cases. It shows the innovative potential of the interactions between the galaninergic and serotonergicsystems to find new strategies and drugs against resistant depression
PB Elsevier
YR 2024
FD 2024
LK https://hdl.handle.net/10630/35297
UL https://hdl.handle.net/10630/35297
LA spa
NO Juan Pedro Pineda-Gómez, Carmelo Millón, Noelia Cantero-García, Marta Flores-Gómez, David Ladrón de Guevara-Miranda, Antonio Flores-Burgess, Zaida Díaz-Cabiale, A new pharmacological strategy against treatment-resistant depression, Progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 136, 2025, 111191, ISSN 0278-5846, https://doi.org/10.1016/j.pnpbp.2024.111191.
NO Funding for open access charge: Universidad de Málaga/ CBUA
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026