Section 9
Chapter 8,475

Differential regulation by N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors of acetylcholine release from the rat striatum in vivo

Giovannini, M.G.; Camilli, F.; Mundula, A.; Bianchi, L.; Colivicchi, M.A.; Pepeu, G.

Neuroscience 65(2): 409-415


ISSN/ISBN: 0306-4522
PMID: 7539896
DOI: 10.1016/0306-4522(94)00503-w
Accession: 008474250

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The modulation of striatal cholinergic neurons by glutamatergic inputs was studied by monitoring the output of acetylcholine collected via a transversal microdialysis probe implanted into the striatum of freely moving rats. A transversal microdialysis membrane was inserted in the striatum and acetylcholine or GABA levels in the dialysate were measured. Acetylcholine levels in the dialysate were quantified by a high-performance liquid chromatography method with an electrochemical detector, while GABA levels were measured by a high-performance liquid chromatography method with a fluorescence detector. The dialysis membrane was perfused with Ringer solution containing 7 mu-M physostigmine sulphate and drugs, dissolved in the perfusion solution, were administered locally via the dialysis membrane. Local administration of the N-methyl-D-aspartate antagonist 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (25-100 mu-M) brought about a decrease in striatal acetylcholine output which was dose-dependent, reversible and partially antagonized by 100 mu-M N-methyl-D-aspartate. On the other hand, local administration of the non-N-methyl-D-aspartate antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline was followed by an increase in acetylcholine output which reached a maximum of about +55% at 12.8 mu-M 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline and was readily reversed when the drug was withdrawn from the perfusion solution. Local administration of the non-N-methyl-D-aspartate receptor agonist (S)-alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (50 and 200 mu-M) decreased acetylcholine output and this effect was reversed by simultaneous perfusion with the GABA antagonist bicuculline (50 mu-M). In one set of experiments the effect of the non-N-methyl-D-aspartate antagonist quisqualate was investigated both on acetylcholine and GABA output from the striatum of the same animal. Quisqualate perfused through the striatum resulted in a decrease in acetylcholine output and a concomitant increase in GABA output. These results demonstrate that the activity of the striatal cholinergic neurons receive a differential modulation by glutamatergic inputs, depending on the type of receptor involved. N-methyl-D-aspartate receptors tonically activate cholinergic neurons and increase acetylcholine output while non-N-methyl-D-aspartate receptors indirectly, via a GABAergic link, decrease acetylcholine output.

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