The release of dopamine from nerve terminals and dendrites of nigrostriatal neurons induced by excitatory amino acids in the conscious rat.
The possible localization of excitatory amino acid (EAA) receptors on dopaminergic neurons was studied by microdialysis in conscious male rats. Varying concentrations of 3 specific EAA agonists, N-methyl-D-aspartate (NMDA), kainate and amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), were infused into the striatum or into the substantia nigra, and the extracellular dopamine (DA) was recorded by the same probe. All 3 compounds induced a dose-dependent increase in both striatal and nigral extracellular DA. Kainate and AMPA were more potent than NMDA. Nigral DA release was stimulated by lower concentrations of kainate and AMPA than striatal DA release. The effects of two concentrations of NMDA and kainate on the release of DA were analyzed in terms of tetrodotoxin (TTX) dependency and sensitivity to ibotenic acid-induced striatal lesion. It appeared that NMDA and kainate stimulated DA release by 3 different mechanisms. The first mechanism is seen at low concentrations of kainate, it fulfills the criteria for a functional receptor-interaction: it is TTX-sensitive and independent of the ibotenic acid lesion. The second mechanism was observed when relatively low concentrations of NMDA stimulate the release of DA; in this effect postsynaptic structures are involved. The third mechanism lacks specificity as it is seen after high concentrations of kainate as well as of NMDA. The latter mechanism is TTX-independent and is probably of a toxic nature. Finally NMDA and kainate were infused into the nigra, whereas DA was recorded with a second probe implanted into the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
Westerink
B H
BH
Department of Medicinal Chemistry, University of Groningen, The Netherlands.
Santiago
M
M
De Vries
J B
JB
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects*
D000596:Amino Acids; D016202:N-Methylaspartate; D007608:Kainic Acid; D004298:Dopamine