Journal of Molecular Neuroscience

, Volume 40, Issue 1–2, pp 172–176 | Cite as

Glutamate–Dopamine Crosstalk in the Rat Prefrontal Cortex is Modulated by Alpha7 Nicotinic Receptors and Potentiated by PNU-120596

  • Phil D. Livingstone
  • Jane A. Dickinson
  • Jayaraman Srinivasan
  • James N. C. Kew
  • Susan Wonnacott


The aim of this study was to explore the modulation by α7 nicotinic receptors (nAChRs) of dopamine and glutamate release in the rat prefrontal cortex where these receptors are implicated in attentional processes and are therapeutic targets for cognitive deficits. The presence of presynaptic α7 nAChRs on glutamate terminals is supported by the ability of the subtype-selective agonist Compound A to evoke [3H]D-aspartate release from synaptosomes: This response was potentiated by the selective allosteric potentiator PNU-120596 and blocked by αbungarotoxin. Compound A also evoked dopamine overflow in the prefrontal cortex in vivo, and this was potentiated by PNU-120596. α7 nAChR-evoked [3H]dopamine release from tissue prisms in vitro was blocked by antagonists of NMDA and AMPA receptors. These data are consistent with a model in which α7 nAChRs present on glutamate terminals increase glutamate release that (1) contributes to presynaptic facilitation and synaptic plasticity and (2) co-ordinately enhances dopamine release from neighbouring boutons.


Dopamine release Microdialysis [3H]D-aspartate release Synaptosomes 


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Copyright information

© Humana Press 2009

Authors and Affiliations

  • Phil D. Livingstone
    • 1
  • Jane A. Dickinson
    • 1
  • Jayaraman Srinivasan
    • 1
  • James N. C. Kew
    • 2
  • Susan Wonnacott
    • 1
  1. 1.Department of Biology & BiochemistryUniversity of BathBathUK
  2. 2.Neurosciences Centre of Excellence for Drug DiscoveryGlaxoSmithKlineHarlowUK

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