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NMDA‐mediated release of glutamate and GABA in the subthalamic nucleus is mediated by dopamine: an in vivo microdialysis study in rats
Author(s) -
Ampe Ben,
Massie Ann,
D’Haens Jean,
Ebinger Guy,
Michotte Yvette,
Sarre Sophie
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04847.x
Subject(s) - microdialysis , nmda receptor , glutamate receptor , dopamine , neurotransmitter , dopaminergic , subthalamic nucleus , chemistry , medicine , endocrinology , pharmacology , biology , central nervous system , biochemistry , receptor , parkinson's disease , disease , deep brain stimulation
The present study investigated the effects of N ‐methyl‐ D ‐aspartic acid·H 2 O (NMDA) on the dopamine, glutamate and GABA release in the subthalamic nucleus (STN) by using in vivo microdialysis in rats. NMDA (100 μmol/L) perfused through the microdialysis probe evoked an increase in extracellular dopamine in the STN of the intact rat of about 170%. This coincided with significant increases in both extracellular glutamate (350%) and GABA (250%). The effect of NMDA perfusion on neurotransmitter release at the level of the STN was completely abolished by co‐perfusion of the selective NMDA‐receptor antagonist MK‐801 (10 μmol/L), whereas subthalamic perfusion of MK‐801 alone had no effect on extracellular neurotransmitter concentrations. Furthermore, NMDA induced increases in glutamate were abolished by both SCH23390 (8 μmol/L), a selective D 1 antagonist, and remoxipride (4 μmol/L), a selective D 2 antagonist. The NMDA induced increase in GABA was abolished by remoxipride but not by SCH23390. Perfusion of the STN with SCH23390 or remoxipride alone had no effect on extracellular neurotransmitter concentrations. The observed effects in intact animals depend on the nigral dopaminergic innervation, as dopamine denervation, by means of 6‐hydroxydopamine lesioning of the substantia nigra, clearly abolished the effects of NMDA on neurotransmitter release at the level of the STN. Our work points to a complex interaction between dopamine, glutamate and GABA with a crucial role for dopamine at the level of the STN.