2026-05-28T23:41:07Zhttps://riuma.uma.es/rest/oai/requestoai:riuma.uma.es:10630/352972026-02-03T10:59:53Zcom_10630_2254col_10630_37953
RIUMA. Repositorio Institucional de la Universidad de Málaga
author
Pineda-Gomez, Juan Pedro
author
Millón-Peñuela, Carmelo
author
Cantero García, Noelia
author
Flores, Marta
author
Ladrón de Guevara-Miranda, David
author
Flores-Burgess, Antonio
author
Díaz-Cabiale, Zaida
2024-11-25T12:39:44Z
2024-11-25T12:39:44Z
2024
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.
https://hdl.handle.net/10630/35297
10.1016/j.pnpbp.2024.111191
Major depressive disorder affects more than 50 million people in the world. However, 50% of patients don’t
respond to two or more drugs or psychotherapeutic treatments, named treatment-resistant depression (TRD). In
this work, we propose a new augmentation treatment against TRD based on combining Fluoxetine (FLX) and the
N-terminal fragment Galanin, GAL(1–15). In Wistar Kyoto (WKY) rats, akin to endogenous depression geneti
cally, 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 knock
down. Also, the 5-HT1AR was analyzed by autoradiography binding in several brain regions. We analyze the
corticosterone levels and a dexamethasone-suppressed corticotropin-releasing hormone stimulation to study the
HPA axis regulation. Our results shows that only the combination of FLX + GAL(1–15) induced antidepressant
effects in the WKY animals in Behavioural tests related to despair. This combination also reduced corticosterone
levels in the WKY animals and modulated the functional characteristics of the serotoninergic receptor 5-HT1A in
the prefrontal cortex. These novel results suggest combining GAL(1–15) with FLX is a new potentiation strategy
in TRD cases. It shows the innovative potential of the interactions between the galaninergic and serotonergic
systems to find new strategies and drugs against resistant depression
spa
Attribution 4.0 Internacional
Fisiología
Depresión
Farmacología
A new pharmacological strategy against treatment-resistant depression
journal article
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A new pharmacological strategy against treatment-resistant depresion.pdf