NMDA and AMPA/kainate glutamatergic agonists increase the extracellular concentrations of GABA in the prefrontal cortex of the freely moving rat: modulation by endogenous dopamine

Brain Research Bulletin
Alberto Del Arco, F Mora

Abstract

Using microdialysis in the prefrontal cortex, this study investigated first the effects of the ionotropic glutamatergic agonists NMDA and AMPA on extracellular concentrations of GABA, and second, the modulation of these effects by increasing endogenous dopamine. NMDA (20, 100, and 500 microM) and AMPA (1, 20, and 100 microM), perfused through the microdialysis probe for 60 min, produced a dose-related increase of extracellular concentrations of GABA in the prefrontal cortex of the awake rat. NMDA 100 and 500 microM produced a maximal increase of extracellular GABA of 150 +/- 38% and 245 +/- 75% of baseline, respectively. AMPA 20 and 100 microM produced a maximal increase of extracellular GABA of 140 +/- 17% and 195 +/- 41% of baseline, respectively. NMDA and AMPA also increased extracellular concentrations of glutamate. Increases of extracellular GABA, and also of glutamate, produced by NMDA (500 microM) and AMPA (100 microM) were significantly blocked by the NMDA antagonist CPP (100 microM) and the AMPA/kainate antagonist DNQX (100 microM), respectively. To investigate whether dopamine modulates the increases of GABA produced by NMDA and AMPA, endogenous dopamine was increased with the dopamine uptake inhibitor nomifensine. No...Continue Reading

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Citations

Apr 20, 2010·Psychopharmacology·Brooke M RobertsStacy A Castner
Dec 25, 2003·Neural Networks : the Official Journal of the International Neural Network Society·F Gregory Ashby, Michael B Casale
Mar 31, 2004·Proceedings of the National Academy of Sciences of the United States of America·Yun Wang, Patricia S Goldman-Rakic
May 5, 2005·The European Journal of Neuroscience·Prathiba Jayaram, Jeffery D Steketee
Jan 18, 2006·European Journal of Pharmacology·Prathiba Jayaram, Jeffery D Steketee
Sep 30, 2006·Analytical Chemistry·Minshan ShouRobert T Kennedy

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