The Adenosinergic System in the Neurobiology of Schizophrenia: Prospective Adenosine Receptor–Based Pharmacotherapy

  • Francisco Ciruela
  • Víctor Fernández-Dueñas
  • Xavier Altafaj
  • Fernando Contreras
  • Antoni Vallano
  • José Manuel Menchón
  • Marta Valle-León


The pharmacotherapy of schizophrenia relies on restoring a dysregulated striatal dopamine and prefrontal cortex glutamate neurotransmission. However, these treatments are usually insufficient to fully cover all the disease symptomatology (i.e., negative and cognitive symptoms). Thus, the search for alternative and/or complementary neurotransmitter systems involved in the etiology of schizophrenia constitutes a big challenge in psychiatry these days. Adenosine, a well known neuromodulator in the central nervous system, has been highlighted because its relationship with both dopaminergic and glutamatergic neurotransmission. Indeed, the disruption of adenosine homeostasis in the adult brain has multiple consequences in the circuitry implicated in the pathophysiology of schizophrenia. Consequently, the “adenosine hypothesis of schizophrenia” foresees that the disruption of adenosine homeostasis within certain brain areas has behavioral consequences resembling schizophrenia symptoms. Thus, it has been postulated that restoring adenosine concentration within the schizophrenia-related brain areas might have beneficial antipsychotic properties. Overall, as adenosine dysfunction can trigger endophenotypes of schizophrenia, the development of drugs targeting the adenosinergic system will definitely constitute a new opportunity for therapeutic intervention in schizophrenia.


Adenosinergic system Adenosine receptors Schizophrenia Adenosine–dopamine–glutamate interactions 



This work was supported by grants SAF2011-24779, Consolider-Ingenio CSD2008-00005 and PCIN-2013-019-C03-03 from Ministerio de Economía y Competitividad and ICREA Academia-2010 from the Catalan Institution for Research and Advanced Studies to F.C. Also, the authors belong to the “Neuropharmacology and Pain” accredited research group (Generalitat de Catalunya, 2009 SGR 232).


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Francisco Ciruela
    • 1
    • 2
  • Víctor Fernández-Dueñas
    • 1
    • 2
  • Xavier Altafaj
    • 1
    • 2
  • Fernando Contreras
    • 3
  • Antoni Vallano
    • 4
    • 5
  • José Manuel Menchón
    • 3
  • Marta Valle-León
    • 4
  1. 1.Francisco Ciruela Pharmacology Unit, Department of Pharmacology, Faculty of MedicineUniversity of Barcelona, Government Pavilion, Llobregat HospitalBarcelonaSpain
  2. 2.Institut de NeurociènciesUniversitat de BarcelonaBarcelonaSpain
  3. 3.Servei de Psiquitria, Hospital Universitari de Bellvitge-IDIBELL, Universitat de Barcelona, CIBERSAM, L’Hospitalet de LlobregatBarcelonaSpain
  4. 4.Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina, IDIBELLUniversitat de Barcelona, L’Hospitalet de LlobregatBarcelonaSpain
  5. 5.Servei de Farmacologia Clínica, Hospital Universitari de Bellvitge-IDIBELL, L’Hospitalet de LlobregatBarcelonaSpain

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