Influencia del receptor 5-HT4 en la depresión y en el mecanismo de acción de los fármacos antidepresivos
- Amigo Riu, Josep
- María Elena Castro Fernández Director
- Álvaro Díaz Martínez Co-director
Defence university: Universidad de Cantabria
Fecha de defensa: 03 November 2017
- María Amor Hurlé González Chair
- Antonio Rodríguez Gaztelumendi Secretary
- Luis Felipe Callado Hernando Committee member
Type: Thesis
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.