The NMDA receptor as a target for cognitive enhancement

Graham L. Collingridge, Arturas Volianskis, Neil Bannister, Grace France, Lydia Hanna, Marion Mercier, Patrick Tidball, Guangyu Fang, Mark W. Irvine, Blaise M. Costa, Daniel T. Monaghan, Zuner A. Bortolotto, Elek Molnár, David Lodge, David E. Jane

Research output: Contribution to journalReview article

143 Scopus citations

Abstract

NMDA receptors (NMDARs) play an important role in neural plasticity including long-term potentiation and long-term depression, which are likely to explain their importance for learning and memory. Cognitive decline is a major problem facing an ageing human population, so much so that its reversal has become an important goal for scientific research and pharmaceutical development. Enhancement of NMDAR function is a core strategy toward this goal. In this review we indicate some of the major ways of potentiating NMDAR function by both direct and indirect modulation. There is good evidence that both positive and negative modulation can enhance function suggesting that a subtle approach correcting imbalances in particular clinical situations will be required. Excessive activation and the resultant deleterious effects will need to be carefully avoided. Finally we describe some novel positive allosteric modulators of NMDARs, with some subunit selectivity, and show initial evidence of their ability to affect NMDAR mediated events. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Original languageEnglish (US)
Pages (from-to)13-26
Number of pages14
JournalNeuropharmacology
Volume64
DOIs
StatePublished - Jan 1 2013

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Keywords

  • Cognitive enhancement
  • Hippocampus
  • LTP
  • NMDA receptor
  • Positive allosteric modulators
  • Synaptic plasticity
  • Synaptic transmission

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Collingridge, G. L., Volianskis, A., Bannister, N., France, G., Hanna, L., Mercier, M., Tidball, P., Fang, G., Irvine, M. W., Costa, B. M., Monaghan, D. T., Bortolotto, Z. A., Molnár, E., Lodge, D., & Jane, D. E. (2013). The NMDA receptor as a target for cognitive enhancement. Neuropharmacology, 64, 13-26. https://doi.org/10.1016/j.neuropharm.2012.06.051