Álvaro Díaz Martínez

  • alvaro.diaz@unican.es
  • 942 200950​
  • Neurobiological Basis of the Mechanism of Action of Drugs acting at the Central Nervous System
  • Principal Investigator
  • Neuropharmacology
  • Department of Cell & Molecular Signalling

Alvaro Díaz is a Senior Lecturer in Pharmacology at the Department of Physiology and Pharmacology of the University of Cantabria (UC) and a research member of Prof. Pazos group at the Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC) and at the CIBERSAM (Centro de Investigación en Red en Salud Mental- Collaborative Research Network in Mental Health) https://www.cibersam.es/grupos/grupo-de-investigacion?id=14245. He obtained a MD degree in June 1986 (UC) and carried out his predoctoral training in the Department of Physiology and Pharmacology, studying the interaction between neuronal calcium channels and opioid receptors in pain signalling and processing, applying behavioural, neurochemical and molecular techniques and obtaining his PhD degree in 1994. To continue his research career in neuropharmacology, he was awarded a postdoctoral position (Welcome Trust, UK; January 1995 to June 1997) in Professor Dickenson´s lab (University College London), where he carried out "in vivo" electrophysiological techniques to study the role of spinal voltage-sensitive calcium channels, imidazoline I2 sites and neuronal nicotinic acetylcholine receptors in acute and persistent nociception. Back to Spain, he worked as a Research Associate (Department of Physiology and Pharmacology, UC 1997/2001) in research contracts with FAES FARMA S.A in studies directed to the "Valuation of active molecules on serotonergic and dopaminergic systems" using radiometric and "in vivo" electrophysiological techniques. In 2002, he obtained a "Ramón y Cajal" research position (Department of Physiology and Pharmacology, UC) to carry out a project dealing with the study of the modifications in serotonergic, noradrenergic and opioid neurotransmission systems in the animal models of depression in neuropathic pain. From 2006 to 2009, he was Associate Professor of Pharmacology in the University of Cantabria (Profesor Contratado Doctor) and in 2009 he was promoted to Senior Lecturer (Profesor Titular). From then until now, he has being involved in projects aimed to study the neurobiology of depression and to evaluate the behavioural, neurochemical and molecular actions of classic and potential antidepressants, using animal models of depression, and different techniques to assess the expression/functionality of receptors, and biomarkers of neurogenesis and neuroplasticity (orcid code: https://orcid.org/0000-0002-8783-4555). He has also carried out contract research projects with the pharmaceutical company Servier S.L. to evaluate the potential antidepressant effects of AMPA modulators. Regarding the academic activity, he is teaching Pharmacology in the Degree of Medicine and the Degree of Nursery, and he belongs to the lecturer's staff of the "Master's Degree in Initiation in Research in Mental Health" (CIBERSAM) and "Master's Degree in Molecular Biology and Medicine" (UC/UPV).


Neurobiological Basis of the Mechanism of Action of Drugs acting at the Central Nervous System


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


mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse

mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-like State in Mouse

Garro-Martínez E, Fullana MN, Florensa-Zanuy E, Senserrich J, Paz V, Ruiz-Bronchal E, Adell A, Castro E, Díaz Á, Pazos Á, Bortolozzi A, Pilar-Cuéllar F.

Int J Mol Sci. 2021 Aug 12;22(16):8671. doi: 10.3390/ijms22168671.

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5-HT 4 Receptors Are Not Involved in the Effects of Fluoxetine in the Corticosterone Model of Depression

Amigo J, Garro-Martinez E, Vidal Casado R, Compan V, Pilar-Cuéllar F, Pazos A, Díaz A, Castro E.

ACS Chem Neurosci. 2021 Jun 2;12(11):2036-2044. doi: 10.1021/acschemneuro.1c00158. Epub 2021 May 11.

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Cannabidiol antidepressant-like effect in the lipopolysaccharide model in mice: Modulation of inflammatory pathways

Florensa-Zanuy E, Garro-Martínez E, Adell A, Castro E, Díaz Á, Pazos Á, Mac-Dowell KS, Martín-Hernández D, Pilar-Cuéllar F.

​Biochem Pharmacol. 2021 Mar;185:114433. doi: 10.1016/j.bcp.2021.114433. Epub 2021 Jan 26.

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Increased vulnerability to impulsive behavior after streptococcal antigen exposure and antibiotic treatment in rats.

Increased vulnerability to impulsive behavior after streptococcal antigen exposure and antibiotic treatment in rats.

Santiago Mora, Elena Martín-González, Ángeles Prados-Pardo, José Joaquín Moreno-Casco, María José López-López, Fuencisla Pilar-Cuellar, Elena Castro, Álvaro Díaz, Pilar Flores, Margarita Moreno

​Brain Behav Immun. 2020 Aug 13:S0889-1591(20)30083-0. doi: 10.1016/j.bbi.2020.08.010. Online ahead of print.

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S 47445 counteracts the behavioral manifestations and hippocampal neuroplasticity changes in bulbectomized mice.

Pilar-Cuellar F, Castro E, Bretin S, Mocaer E, Pazos Á, Díaz Á.

​Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jul 13;93:205-213. doi: 10.1016/j.pnpbp.2019.04.005. Epub 2019 Apr 10.​

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β-Catenin Role in the Vulnerability/Resilience to Stress-Related Disorders Is Associated to Changes in the Serotonergic System.

Garro-Martínez E, Vidal R, Adell A, Díaz Á, Castro E, Amigó J, Gutiérrez-Lanza R, Florensa-Zanuy E, Gómez-Acero L, Taketo MM, Pazos Á, Pilar-Cuéllar F.

Mol Neurobiol. 2019 Dec 10. doi: 10.1007/s12035-019-01841-0. [Epub ahead of print]

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The endocannabinoid system in mental disorders: Evidence from human brain studies. Biochem Pharmacol.

Ibarra-Lecue I, Pilar-Cuéllar F, Muguruza C, Florensa-Zanuy E, Díaz Á, Urigüen L, Castro E, Pazos A, Callado LF.

​2018 Nov;157:97-107. doi: 10.1016/j.bcp.2018.07.009. Epub 2018 Jul 17.

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Potentiation of morphine-induced antinociception and locomotion by citalopram is accompanied by anxiolytic-like effects.

Varela MJ, Acanda de la Rocha AM, Díaz A, Lopez-Gimenez JF.

​Pharmacol Biochem Behav. 2017 Dec;163:83-89. doi: 10.1016/j.pbb.2017.10.003. Epub 2017 Oct 10.

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Behavioral, neurochemical and molecular changes after acute deep brain stimulation of the infralimbic prefrontal cortex.

Jiménez-Sánchez L, Linge R, Campa L, Valdizán EM, Pazos Á, Díaz Á, Adell A. Neuropharmacology. 2016 Sep;108:91-102. doi: 10.1016/j.neuropharm.2016.04.020

​https://www.ncbi.nlm.nih.gov/pubmed/?term=Behavioral%2C+neurochemical+and+molecular+changes+after+acute+deep+brain+stimulation+of+the+infralimbic+prefrontal+cor

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The absence of 5-HT4 receptors modulates depression- and anxiety-like responses and influences the response of fluoxetine in olfactory bulbectomised mice: Adaptive changes in hippocampal neuroplasticity markers and 5-HT1A autoreceptor.

Amigó J, Díaz A, Pilar-Cuéllar F, Vidal R, Martín A, Compan V, Pazos A, Castro E.

​Neuropharmacology. 2016 Dec;111:47-58. doi: 10.1016/j.neuropharm.2016.08.037. Epub 2016 Aug 30.​

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Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors.

Linge R, Jiménez-Sánchez L, Campa L, Pilar-Cuéllar F, Vidal R, Pazos A, Adell A, Díaz Á. Neuropharmacology. 2016 Apr;103:16-26. doi: 10.1016/j.neuropharm.2015.12.017.

[PubMed]

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Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors.

Linge R, Jiménez-Sánchez L, Campa L, Pilar-Cuéllar F, Vidal R, Pazos A, Adell A, Díaz Á.

​Neuropharmacology. 2016 Apr;103:16-26. doi: 10.1016/j.neuropharm.2015.12.017. Epub 2015 Dec 19.

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Serotonin 5-HT4 receptors: A new strategy for developing fast acting antidepressants?

Vidal R, Castro E, Pilar-Cuéllar F, Pascual-Brazo J, Díaz A, Rojo ML, Linge R, Martín A, Valdizán EM, Pazos A.

​Curr Pharm Des. 2014;20(23):3751-62.

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Signaling pathways involved in antidepressant-induced cell proliferation and synaptic plasticity.

Pilar-Cúellar F, Vidal R, Díaz A, Castro E, dos Anjos S, Vargas V, Romero B, Valdizán EM.

​Curr Pharm Des. 2014;20(23):3776-94.​

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Ángel Pazos Carro (IP)

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Elena Castro Fernández

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Daniel Coca De Pablo

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Eva Florensa Zanuy

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Mª Fuencisla Pilar Cuéllar

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Júlia Senserrich Guerrero

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