Influencia del receptor 5-HT4 en la depresión y en el mecanismo de acción de los fármacos antidepresivos

  1. Amigo Riu, Josep
Supervised by:
  1. María Elena Castro Fernández Director
  2. Álvaro Marcelino Díaz Martínez Co-director

Defence university: Universidad de Cantabria

Fecha de defensa: 03 November 2017

Committee:
  1. María Amor Hurlé González Chair
  2. Antonio Rodríguez Gaztelumendi Secretary
  3. Luis Felipe Callado Hernando Committee member

Type: Thesis

Teseo: 513584 DIALNET lock_openUCrea editor

Abstract

The main objective of this thesis is to clarify the role of 5-HT4 receptors in depression and in the mechanism of action of antidepressant drugs. 5-HT4 KO mice show an innate anxiety and anhedonia, but a similar susceptibility than WT mice to the behavioural features of animal models of depression (chronic administration of corticosterone and bilateral olfactory bulbectomy). Chronic treatment with RS67,333, a partial agonist of the 5-HT4 receptor, induces an anxiolytic effect in both animal models and an antianhedonic effect only in the corticosterone model. In contrast, chronic administration of fluoxetine produces an antidepressant effect in both animal models. Our in vitro studies demonstrate that both drugs have differential actions on neurochemical (5-HT1A receptor functionality) and molecular (mRNA expression coding for BDNF, Arc, and TrkB) markers related to depression and its therapeutics.