Endogenous excitatory amino acids tonically stimulate striatal acetylcholine release through NMDA but not AMPA receptors.
The effect of stimulation and blockade of excitatory amino acid receptors on striatal acetylcholine release was examined using in vivo microdialysis in awake, freely moving rats. Local perfusion with the NMDA receptor antagonists CPP and MK-801 reduced striatal acetylcholine release, while NMDA itself enhanced striatal acetylcholine release. Co-perfusion with MK-801 blocked the NMDA-induced increase in acetylcholine release. The AMPA/kainate antagonists NBQX and GYKI 52466 alone did not decrease striatal acetylcholine release, although AMPA increased acetylcholine release. Co-perfusion with NBQX reduced the AMPA-induced elevation in acetylcholine release. These findings suggest that endogenous excitatory amino acids tonically stimulate striatal acetylcholine release through NMDA but not AMPA receptors.
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
J J
JJ
Anderson
S
S
Kuo
T N
TN
Chase
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004563:Electrochemistry; D018846:Excitatory Amino Acids / Q000502:physiology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018846:Excitatory Amino Acids; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D000109:Acetylcholine