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

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


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.


Prepulse Inhibition Sucrose Preference Sensorimotor Gating Positive Allosteric Modulator mGluR5 Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer India 2016

Authors and Affiliations

  • Derek K. Tracy
    • 1
    • 2
  • Nicola Smallcombe
    • 2
  • Farah Tiwana
    • 2
  • Judith Fosbraey
    • 2
  • Kyra-Verena Sendt
    • 2
  • Sukhwinder S. Shergill
    • 3
    • 2
  1. 1.Crisis, Inpatient, and Rehabilitation ServicesOxleas NHS Foundation TrustLondonUK
  2. 2.Cognition Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, the Institute of PsychiatryKing’s College LondonLondonUK
  3. 3.The National Psychosis UnitSouth London and Maudsley NHS Foundation TrustLondonUK

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