Y. Ikarashi et al., DIRECT REGULATION OF ACETYLCHOLINE-RELEASE BY N-METHYL-D-ASPARTIC ACID RECEPTORS IN RAT STRIATUM, Brain research, 795(1-2), 1998, pp. 215-220
The aziridinium ion of ethylcholine (AF64A), a cholinergic neurotoxin,
was injected into the right striatum of a rat. The unilateral injecti
on of 10 nmol AF64A reduced the activity of choline acetyltransferase
(CAT) and the tissue content of acetylcholine (ACh) in the striatum. T
he striatal contents of dopamine (DA), norepinephrine (NE), 5-hydroxyi
ndoleacetic acid (5-HIAA) and gamma-aminobutyric acid (GABA) were unch
anged. These results suggest that the cholinospecificity in the striat
al lesion was induced by the 10 nmol dose of AF64A. The number of N-me
thyl-D-aspartic acid (NMDA) receptors in the striatum treated with 10
nmol AF64A was determined by a specific binding assay using /-)-3-(2-c
arboxypiperazin-4-yl)propyl-1-phosphonic acid ([H-3]CPP), a selective
ligand for NMDA receptors. The number of the NMDA receptors decreased
significantly in the injected area. On the other hand, in a microdialy
sis using normal rats, the perfusion of 50 mu M NMDA into the striatum
increased ACh release. The perfusion of 100 mu M MK801 which is the s
pecific and non-competitive NMDA receptor antagonist, decreased the ba
sal levels of ACh release and blocked NMDA-elicited ACh release. Taken
together, the present results strongly suggest that a population of N
MDA receptors exists on cholinergic interneurons within the striatum,
and it directly regulates ACh release. (C) 1998 Elsevier Science B.V.
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