Influence of excitatory amino acid receptor subtypes on the electrophysiological activity of dopaminergic and nondopaminergic neurons in rat substantia nigra.
In vivo electrophysiological recording methods were used to evaluate the effects of selective and nonselective agonists for excitatory amino acid (EAA) receptor subtypes on the activity of dopaminergic (DA) and nondopaminergic (non-DA) neurons in the substantia nigra of chloral hydrate-anesthetized rats. Microiontophoretic administration of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), 2-carboxy-4-(1-methyl-ethenyl)-3-pyrrolidinacetate (kainate), N-methyl-D-aspartate (NMDA) and glutamate excited neurons with an apparent rank order of potency of AMPA = kainate = glutamate > NMDA on DA neurons, and AMPA = kainate > glutamate = NMDA on non-DA neurons. These agonists also changed the firing pattern of DA neurons, which displayed an increase in burst-firing and a reduction in the regularity of the firing pattern. Regularity of firing was indexed by the variation coefficient of a sample of interspike intervals. The apparent potencies of the four agonists to increase burst-firing and variation coefficient were similar to their potencies to increase neuronal firing rate. Blockade of NMDA receptor function by coiontophoresis of 5R,10S-(+/-)-5-methyl-10,11-dihydro-5H-dibenzo[and]cyclohepten-5,1 0-imine hydrogen maleate (MK-801), a selective noncompetitive NMDA antagonist, did not alter kainate-induced changes in firing rate and firing pattern, which indicated that kainate-induced increases in burst-firing were not dependent on concomitant NMDA receptor activation by endogenous excitatory amino acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhang
J
J
Department of Psychiatry, Wayne State University School of Medicine, Detroit, Michigan.
Chiodo
L A
LA
Freeman
A S
AS
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007478:Iontophoresis; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017459:Receptors, Amino Acid / Q000145:classification* / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D005971:Glutamates; D017459:Receptors, Amino Acid; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid; D004298:Dopamine