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The Glutamate mGluR5 Receptor as a Pharmacological Target to Enhance Cognitive Function: Emerging Evidence from Psychosis Models

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Abstract

Schizophrenia is a profoundly disabling condition affecting approximately 1% of the population. Although often defined by the presence of so-called ‘positive’ symptoms of hallucinations and delusions, sufferers are typically more affected by the more insidious cognitive and ‘negative’ (social withdrawal and amotivational) symptoms. The dopaminergic hypothesis has been a dominant neurobiological model, particularly as the majority of current antipsychotic medications act upon dopamine pathways, but it is notably incomplete; noteworthy, existing medications have, at best, very limited effects upon cognitive deficits. The glutamatergic (Glu) system has attracted attention in recent times as a putative target, though modulation of this ubiquitous system in the brain is not without danger; to this end the metabotropic mGluR5 receptor has emerged as a possible mechanism through which safe Glu modification might be effected. Most data at this time have emerged from animal model studies; these are interesting, with positive results, but need replication in human samples. At present, the future use of mGluR5 modifying drugs has yet to be established.

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Authors and Affiliations

  1. Crisis, Inpatient, and Rehabilitation Services, Oxleas NHS Foundation Trust, London, UK

    Derek K. Tracy

  2. Cognition Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, the Institute of Psychiatry, King’s College London, London, UK

    Derek K. Tracy, Nicola Smallcombe, Farah Tiwana, Judith Fosbraey, Kyra-Verena Sendt & Sukhwinder S. Shergill

  3. The National Psychosis Unit, South London and Maudsley NHS Foundation Trust, London, UK

    Sukhwinder S. Shergill

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  1. Derek K. Tracy
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  2. Nicola Smallcombe
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  3. Farah Tiwana
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  4. Judith Fosbraey
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  5. Kyra-Verena Sendt
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  6. Sukhwinder S. Shergill
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Correspondence to Derek K. Tracy .

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  1. Vice-Rectorate for Research and Sci, Camilo José Cela University Vice-Rectorate for Research and Sci, Madrid, Spain

    Francisco López-Muñoz

  2. International Medical Sciences Research Study Center, Sri Sathya Sai Medical Educational & Research Foundation, Coimbatore, India

    Venkataramanujam Srinivasan

  3. Department of Neurosciences and Ima, University of Chieti Department of Neurosciences and Ima, Italy, Italy

    Domenico de Berardis

  4. Department of Biomedical Sciences (Pharmacology Area), University of Alcalá, Madrid, Spain

    Cecilio Álamo

  5. Department of Neuropsychiatry, Kyushu University, Fukuoka, Japan

    Takahiro A. Kato

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Tracy, D.K., Smallcombe, N., Tiwana, F., Fosbraey, J., Sendt, KV., Shergill, S.S. (2016). The Glutamate mGluR5 Receptor as a Pharmacological Target to Enhance Cognitive Function: Emerging Evidence from Psychosis Models. In: López-Muñoz, F., Srinivasan, V., de Berardis, D., Álamo, C., Kato, T. (eds) Melatonin, Neuroprotective Agents and Antidepressant Therapy. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2803-5_43

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