Principal Investigator:

Dr. Angel Pazos, Full Professor of Pharmacology (University of Cantabria)

 

Other personnel:

Dr. Elena Castro Fernández, Associate Professor

Dr. Alvaro Díaz Martínez, Associate Professor

Dr. Elsa Valdizán Ruiz, Associate Professor

Dr. Beatriz Martinez Villayandre, Postdoctoral

Alejandro Aguilera Román, Predoctoral

Raquel Linge Méndez, Predoctoral

Begoña Treceño Dalmau, Predoctoral

Verónica Inés Vargas, Predoctoral

Helena Blanco Gómez, Laboratory technician

Alicia Martín Rebollo, Laboratory technician

Rebeca Madureira Rivero, Laboratory technician

Beatriz Romero Presno, Laboratory technician

Isabel Ruiz Alechiguerra, Laboratory technician

Research lines:

The main research line of the group deals with the neurochemical and neuroplastic signals involved in the pathogeny of neuropsychiatric diseases (major depression, schizophrenia) and, associated to that,  in the mechanism of action of antidepressant and antipsychotic  drugs. The goals of our neuropharmacological research include the study of:

-   The role of monoaminergic systems (manly serotonin, 5-HT) in these psychiatric diseases and their modulation by chronic administration of antidepressants, with special interest on 5-HT1 and 5-HT4 receptors

-   The identification of brain  neuroplastic and neurogenetic pathways that could be targets of new pharmacological strategies for the treatment of depression and schizophrenia (b-catenin, BDNF)

-   The relationship between central aminergic pathways and recently identified neuromodulator systems (endocannabinoid, mTOR) and its relevance n major depression

For this purpose, studies in laboratory animals, models of depression and psychosis, and in blood and postmortem samples from depressed and schizophrenic patients are carried out. Behavioural, pharmacological (in vivo assays, receptor labeling), cell biology (immunocytochemistry, neurogenesis), biochemical (second messengers, G proteins), electrophysiological (in vivo and slice recordings) and molecular approaches (gen silencing, transfected receptors) are used.

Other sublines of research of the group include:

-   The neurobiological basis of the analgesic responses induced by antidepressants

-    The identification of the intracellular signaling mechanisms associated to 5-HT receptor subtypes

-   The analysis of polymorphisms for proteins of relevance for the etiopathogeny of depressive disorders

-    The characterization of animal models of psychiatric disorders

 

Funding:

             CICYT, Ministerio de Ciencia e Innovación. Fármacos antidepresivos y dianas de señalización intracelular: implicación de mecanismos de proliferación (SAF07-61862). Octubre 2007-Septiembre 2012

Neuroplasticity mechanisms involved in the fast antidepressant response of 5-HT₄ receptor agonists: role of the Wnt-b-catenin and mTOR pathways (SAF2011-25020 ). Enero 2012-Diciembre 2014.

Instituto de Salud Carlos III. CIBER de Salud Mental, 2009-

               

             Programa ZENIT,  Ministerio de Ciencia e Innovación (con BrainCo y FaesFarma SA).Nuevas aproximaciones en el tratamiento de las enfermedades del sistema nervioso. Enero 2010-Diciembre 2012

 

Relevant publications (last 10 years)

Castro M.E., Díaz A., Olmo E. Del, Pazos A. Chronic fluoxetine induces opposite changes in G protein coupling at pre and psotsynaptic 5-HT_1A receptors in rat brain. Neuropharmacology, 44: 93-101, 2003.

 

Valdizán E.M., Gutiérrez O., Pazos A. Adenylate cyclase activity in postmortem brain of suicide subjects: reduced response to β-adrenergic stimulation. Biol. Psychiatry, 54: 1457-1464, 2003.

 

Mato S., Chevaleyre V., Robbe D., Pazos A., Castillo P.E., Manzoni O. A single in vivo exposure to delta 9-THC blocks endocannabinoid-mediated synaptic plasticity. Nature Neuroscience, 7: 585-587, 2004.

 

Adell A., Castro E., Celada P., Bortolozzi A., Pazos A., Artigas F. Strategies for producing more rapidly acting antidepressants. Drug Discovery Today, 10: 578-585, 2005.

 

Mato S., Aso E., Castro E., Martín M., Valverde O., Maldonado R., Pazos A. CB₁ knockout mice display impaired functionality of 5-HT_1A and 5-HT_2A receptors. J. Neurochem., 103: 2111-2120, 2007.

 

Mostany R., Valdizán E.M. Pazos, A. A role for nuclear β-catenin in SNRI antidepressant-induced hippocampal cell proliferation. Neuropharmacology, 55: 18-26, 2008.

 

Rodriguez-Gaztelumendi A., Rojo M.L., Pazos A., Díaz A. Altered CB₁ receptor-signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine. J. Neurochem., 108: 1423-1433, 2009.

 

Vidal R., Valdizán E.M., Vilaró T., Pazos A., Castro E. Reduced signal transduction by 5-HT₄ receptors after long-term venlafaxine treatment in rats. Br. J. Pharmacol., 161: 695-706, 2010.

Valdizán E.M., Díez-Alarcia R., González-Maeso J., Pilar-Cuéllar F., García-Sevilla J.A., Meana J.J., Pazos A.  a₂-adrenoceptor functionality in postmortem frontal cortex of depressed suicide victims. Biol. Psychiatry, 68: 869-872, 2010.

Vidal R., Pilar-Cuéllar F., Dos Anjos S., Linge R., Treceño B., Vargas V., Rodriguez-Gaztelumendi A., Mostany R., Castro E., Diaz A., Valdizán E.M., Pazos A. New strategies in the development of antidepressants: towards the modulation of neuroplasticity pathways. Current Pharmacological Design,

Pilar-Cuéllar F., Vidal R.,  Pazos A. Subchronic treatment with fluoxetine and the 5-HT_2A antagonist ketanserin upregulates hippocampal BDNF and β-catenin in parallel with antidepressant-like effect. Br. J. Pharmacol., (submitted).

 

Contact:

Angel Pazos Carro

Instituto de Biomedicina y Biotecnología de Cantabria

Cardenal Herrera Oria s/n

39011 Santander

Tel. 942 201985       942 201964

pazosa@unican.es