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Involvement of intrinsic cholinergic and GABAergic innervation in the effect of NMDA on striatal dopamine efflux and metabolism as assessed by microdialysis studies in freely moving rats
Author(s) -
Whitehead K. J.,
Rose S.,
Jenner P.
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01702.x
Subject(s) - bicuculline , dopamine , homovanillic acid , chemistry , microdialysis , endocrinology , medicine , 3,4 dihydroxyphenylacetic acid , neurotransmitter , pharmacology , gabaergic , cholinergic , nmda receptor , striatum , gabaa receptor , biology , inhibitory postsynaptic potential , receptor , biochemistry , serotonin
Microdialysis perfusion was used to study the participation of striatal cholinergic and γ‐aminobutyric acid‐ergic (GABAergic) neurotransmission in basal and N ‐methyl‐ d ‐aspartate (NMDA) receptor‐modulated dopamine release and metabolism in the striatum of the freely moving rat. Reverse dialysis of atropine (1–50 µ m ) induced a concentration‐related increase in dopamine efflux and decrease in 3,4‐dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) efflux. (+)‐Bicuculline (10–100 µ m ) similarly increased dopamine efflux, but was without consistent effect on metabolite efflux. Reverse dialysis of NMDA (1 m m ) evoked an approximately twofold increase in dopamine efflux and decreased DOPAC and HVA efflux to 30–40% of basal levels. The effect of NMDA on dopamine efflux was completely abolished by coadministration of tetrodotoxin (TTX; 1 µ m ) or atropine (10 µ m ), and markedly potentiated (approximately fourfold) by coadministration of (+)‐bicuculline (50 µ m ). The NMDA‐induced decrease in dopamine metabolite efflux was inhibited by coadministration of TTX or (+)‐bicuculline, but was unaffected by atropine. Our data suggest that dopamine release in the striatum is subject to both cholinergic and GABAergic tonic inhibitory mechanisms mediated through muscarinic and GABA A receptors, respectively. Furthermore, NMDA‐stimulated dopamine release also involves obligatory cholinergic facilitation and an inhibitory GABAergic component mediated through these respective receptors.