Glutamate regulates the spontaneous and evoked release of dopamine in the rat striatum.
Resting and evoked extracellular dopamine levels in the striatum of the anesthetized rat were measured by fast-scan cyclic voltammetry in conjunction with carbon fiber microelectrodes. Identification of the substance detected in vivo was achieved by inspection of background-subtracted voltammograms. Intrastriatal microinfusion of kynurenate, a broad-spectrum antagonist of ionotropic glutamate receptors, caused a decrease in the resting extracellular level of dopamine. The kynurenate-induced decrease was unaffected by systemic pretreatment with pargyline, an inhibitor of monoamine oxidase, but was significantly attenuated by systemic pretreatment with alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase. Although glutamate by itself did not affect resting extracellular dopamine levels, glutamate did attenuate the kynurenate-induced decrease. Kynurenate decreased dopamine release in response to electrical stimulation of the medial forebrain bundle, an effect that was also attenuated by glutamate. These results suggest that both spontaneous and evoked dopamine release in the rat striatum are under the local tonic excitatory influence of glutamate. Interactions between central dopamine and glutamate systems that have been implicated in the etiologies of Parkinson's disease, schizophrenia, stress, and substance abuse. The precise nature of those interactions, however, remains a matter of some controversy.
Department of Chemistry, University of Pittsburgh, PA 15260, USA.
N V
NV
Kulagina
M J
MJ
Zigmond
A C
AC
Michael
D000818:Animals; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D008996:Monoamine Oxidase Inhibitors; D018698:Glutamic Acid; D019805:alpha-Methyltyrosine; D010293:Pargyline; D007736:Kynurenic Acid