F. Blanchet et al., N-METHYL-D-ASPARTATE-EVOKED RELEASE OF [H-3] ACETYLCHOLINE IN STRIATAL COMPARTMENTS OF THE RAT - REGULATORY ROLES OF DOPAMINE AND GABA, Neuroscience, 81(1), 1997, pp. 113-127
The N-methyl-D-aspartate-evoked release of [H-3]acetylcholine previous
ly formed from [H-3]choline was estimated in striosome- (identified by
[H-3]naloxone binding) or matrix-enriched areas of the rat striatum u
sing an ill vitro microsuperfusion procedure. Experiments were perform
ed in either the absence or the presence of dopaminergic and/or GABAer
gic receptor antagonists. Although the cell bodies of the cholinergic
interneurons were mainly found in the matrix, in the absence of magnes
ium, Iv-methyl-D-aspartate (50 mu M) stimulated the release of [H-3]ac
etylcholine in both striatal compartments: These responses were blocke
d by either magnesium, dizocilpine maleate, 7-chlorokynurenate or tetr
odotoxin. N-Methyl-D-aspartate responses were concentration-dependent,
but the 1 mM N-methyl-D-aspartate response was higher in striosomes t
han in the matrix. The co-application of D-serine (10 mu M) enhanced t
he 10 mu M iv-methyl-D-aspartate response in both compartments, but re
duced those induced by 1 mM N-methyl-D-aspartate, this reduction being
higher in striosomes. The blockade of dopaminergic transmission with
the D-2 and D-1 dopaminergic receptor antagonists, (-)-sulpiride (1 mu
M) and SCH23390 (1 mu M), was without effect on the 50 mu M N-methyl-
D-aspartate-evoked release of [3H]acetylcholine, but markedly enhanced
the 1 mM N-methyl-D-aspartate+D-serine-evoked response in striosomes
and to a lesser extent in the matrix. Disinhibitory responses of simil
ar amplitude were observed not only in striosomes but also in the matr
ix when (-)-sulpiride was used alone, while SCH23390 alone enhanced th
e 1 mM N-methyl-D-aspartate+D-serine response only in striosomes and t
o a lower extent than (-)sulpiride. These results indicate that D-2 re
ceptors are mainly involved in the inhibitory effect of dopamine on th
e 1 mM N-methyl-D-aspartate+D-serine-evoked release of [H-3]acetylchol
ine. They also show that the stimulation of D-1 receptors can either r
educe (striosomes) or enhance (matrix) this response, since in the lat
ter case the effect induced by the combined application of the D-1 and
D-2 receptor antagonists was smaller than that observed with the D-2
receptor antagonist alone. Indicating that released GABA facilitates N
-methyl-D-aspartate responses, the blockade of GABA(A) receptors with
bicuculline (5 mu M) reduced the 50 mu M N-methyl-D-aspartate-evoked r
elease of [H-3]acetylcholine in both striatal compartments and the 1 m
M N-methyl-D-aspartate+D-serine response in the matrix. These effects
result from an inhibition by GABA of the evoked release of dopamine, s
ince the reducing effects of bicuculline on iv-methyl-D-aspartate resp
onses were not observed under the complete blockade of dopaminergic tr
ansmission by the D-1 and D-2 receptor antagonists. Further demonstrat
ing a facilitatory role of GABA in the control of N-methyl-D-aspartate
-evoked release of [H-3]acetylcholine, in the presence of bicuculline,
(-)-sulpiride and SCH23390 alone or in combination enhanced, in both
compartments, the responses induced not only by 1 mM N-methyl-D-aspart
ate+D-serine, but also by 50 mu M N-methyl-D-aspartate. (C) 1997 IBRO.
Published by Elsevier Science Ltd.