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In Vitro Evidence for Increased Facilitation of Striatal Acetylcholine Release via Pre‐ and Postsynaptic NMDA Receptotors in Hemiparkinsonian Rats
Author(s) -
Marti M.,
Sbrenna S.,
Fuxe K.,
Bianchi C.,
Beani L.,
Morari M.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.720875.x
Subject(s) - acetylcholine , nmda receptor , striatum , dopamine , chemistry , postsynaptic potential , substantia nigra , excitatory postsynaptic potential , endocrinology , neuroscience , medicine , biology , inhibitory postsynaptic potential , dopaminergic , biochemistry , receptor
: The NMDA‐evoked acetylcholine release from striatalslices and synaptosomes was investigated in rats subjected to unilateralinjection of 6‐hydroxydopamine into the substantia nigra. In slices preparedfrom the striatum contralateral to the lesion, the NMDA‐evoked endogenousacetylcholine release was not significant at 10 μ M NMDA andmaximal at 100 μ M NMDA (124 ± 19%). Conversely, in slicestaken from the dopamine‐depleted striatum, NMDA was effective even at 10μ M (41 ± 4%), and at 100 μ M (196 ± 24%)efficacy was nearly doubled. In synaptosomes prepared from the contralateralstriatum, NMDA maximally stimulated 20 m M KCl‐induced endogenousacetylcholine release at 1 μ M (66 ± 5.1%), with lowerconcentrations (0.01‐0.1 μ M ) being ineffective. Conversely, insynaptosomes prepared from the dopamine‐depleted striatum, NMDA maximallyenhanced the K + ‐evoked acetylcholine release at 0.1 μ M (118 ± 12.4%). Concentration‐response curves of NMDA‐evoked acetylcholine release in sham‐operated rats could be superimposed on those observed in the contralateral striatum of the 6‐hydroxydopamine‐lesioned animals. The present data support the view of an increased glutamatergic regulation of striatal acetylcholine release via pre‐ and postsynaptic NMDA receptors during Parkinson's disease.