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Excitatory amino acid‐induced excitation of dopamine‐containing neurons in the rat substantia nigra: Modulation by kynurenic acid
Author(s) -
Wu HuiQiu,
Schwarcz Robert,
Shepard Paul D.
Publication year - 1994
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890160307
Subject(s) - kynurenic acid , nmda receptor , excitatory postsynaptic potential , chemistry , ampa receptor , substantia nigra , cnqx , glutamate receptor , excitatory amino acid antagonists , dopamine , pharmacology , medium spiny neuron , neuroscience , biophysics , biochemistry , receptor , striatum , biology , dopaminergic
Kynurenic acid (KYNA), an endogenous antagónist of ionotropic excitatory amino acid (EAA) receptors, was tested for its ability to modulate N‐methyl‐D‐aspartate (NMDA)‐ and α‐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 μ) or AMPA (0.5–10 μ) 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 glycino (GLY) (up to 100 μ) to the bathing solution had no effect on either basal firing rate or the increase in activity produced by NMDA. KYNA (10 μ–1 mM) antagonized the excitatory effects of both NMDA (15 μ) and AMPA (3 μ) in a concentration‐dependent fashion (IC50: 102 μ and 64 μ, respectively) without affecting basal firing rate. Perfusion of tissue slices with a modified Ringer's solution containing low Mg 2+ (0.12 mM) increased NMDA‐induced excitation but did not affect the antagonist properties of KYNA. D‐serine (100 μ) reversed the ability of KYNA to block the excitatory effects of NMDA, suggesting that KYNA attenuates NMDA‐induced excitation of SNc DA neurons via blockade of the GLY allosteric site on the; NMDA receptor. The ability of KYNA to modulate the excitatory effects of both NMDA and non‐NMDA agonists implies that endogenous KYNA may play a physiological role it regulating DA cell excitability. © 1994 Wiley‐Liss, Inc.