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Contact

Dr. Ángel Pazos Carro


Phone: (+34) 942 206799 ext. 136 / Fax :(+34) 942 266399

Email: pazosa@unican.es

Mailing address: IBBTEC. C/ Albert Einstein 22, PCTCAN, 39011 Santander

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Neurobiological basis of the mechanism of action of drugs acting at the central nervous system

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Principal Investigator

Dr. Ángel Pazos, Full Professor of Pharmacology


Other personnel

  • Dr. Elena Castro Fernández, Associate Professor
  • Dr. Alvaro Díaz Martínez, Associate Professor
  • Fuencisla Pilar Cuéllar, Postdoctoral
  • Eva Florensa Zanuy, Predoctoral
  • Rocío Luque Jimenez, administrative staff


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. Cannabidiol como acelerador de la respuesta farmacológica antidepresiva: una vía hacia la identificación de los mecanismos celulares implicados en la depresión (SAF2015-67457-R). Enero 2016-Diciembre 2018.
  • 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)

  • 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.
  • 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.
  • Mato S., Aso E., Castro E., Martín M., Valverde O., Maldonado R., Pazos A. CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A 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.
  • Mato S., Aso E., Castro E., Martín M., Valverde O., Maldonado R., Pazos A. CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A receptors. J. Neurochem., 103: 2111-2120, 2007.
  • 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., 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.
  • 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.
  • Castro M.E., Díaz A., Olmo E. Del, Pazos A. Chronic fluoxetine induces opposite changes in G protein coupling at pre and psotsynaptic 5-HT1A receptors in rat brain. Neuropharmacology, 44: 93-101, 2003.