Excitatory amino acid-induced excitation of dopamine-containing neurons in the rat substantia nigra: modulation by kynurenic acid

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H Q WuP D Shepard

Abstract

Kynurenic acid (KYNA), an endogenous antagonist of ionotropic excitatory amino acid (EAA) receptors, was tested for its ability to modulate N-methyl-D-aspartate (NMDA)- and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-induced excitation of dopamine (DA)-containing neurons in the zona compacta of the rat substantia nigra (SNc). Experiments were conducted using extracellular recording techniques in conjunction with an in vitro brain slice preparation. Bath application of NMDA (1-20 microM) or AMPA (0.5-10 microM) produced a concentration-dependent increase in the firing rate of SNc DA neurons but had no effect on firing pattern. The highest concentration of both agonists produced a rapid and reversible cessation of activity that was attributed to acute induction of depolarization block. Addition of glycine (GLY) (up to 100 microM) to the bathing solution had no effect on either basal firing rate or the increase in activity produced by NMDA. KYNA (10 microM-1 mM) antagonized the excitatory effects of both NMDA (15 microM) and AMPA (3 microM) in a concentration-dependent fashion (IC50:102 microM and 64 microM, respectively) without affecting basal firing rate. Perfusion of tissue slices with a modified Ringer's s...Continue Reading

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Citations

Mar 24, 1997·The Journal of Comparative Neurology·S BischoffS Heinemann
Jul 26, 2011·Journal of Neural Transmission·Vilma GabbayLeonard Liebes
Jul 1, 1997·Neuroscience and Biobehavioral Reviews·L T MeltzerK A Serpa
Dec 23, 1999·Current Opinion in Neurobiology·S T KitaiR Scroggs
Dec 18, 2008·The European Journal of Neuroscience·Yasushi Shimo, Thomas Wichmann
Apr 16, 2013·Pharmacology, Biochemistry, and Behavior·Kyle S L RobinsonAllan V Kalueff
Mar 25, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Taban SeifF Woodward Hopf

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