The N-methyl-D-aspartate-evoked release of [H-3]acetylcholine previously formed from [H-3]choline was estimated in striosome- (identified by [H-3]naloxone binding) or matrix-enriched areas of the rat striatum using an in vitro microsuperfusion procedure. Experiments were performed in either the absence or the presence of dopaminergic and/or GABAergic receptor antagonists. Although the cell bodies of the cholinergic interneurons were mainly found in the matrix, in the absence of magnesium, Iv-methyl-D-aspartate (50 mu M) stimulated the release of [H-3]acetylcholine in both striatal compartments: These responses were blocked by either magnesium, dizocilpine maleate, 7-chlorokynurenate or tetrodotoxin. N-Methyl-D-aspartate responses were concentration-dependent, but the 1 mM N-methyl-D-aspartate response was higher in striosomes than in the matrix. The co-application of D-serine (10 mu M) enhanced the 10 mu M iv-methyl-D-aspartate response in both compartments, but reduced 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 similar amplitude were observed not only in striosomes but also in the matrix when (-)-sulpiride was used alone, while SCH23390 alone enhanced the 1 mM N-methyl-D-aspartate+D-serine response only in striosomes and to a lower extent than (-)sulpiride. These results indicate that D-2 receptors are mainly involved in the inhibitory effect of dopamine on the 1 mM N-methyl-D-aspartate+D-serine-evoked release of [H-3]acetylcholine. They also show that the stimulation of D-1 receptors can either reduce (striosomes) or enhance (matrix) this response, since in the latter 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 release of [H-3]acetylcholine in both striatal compartments and the 1 mM N-methyl-D-aspartate+D-serine response in the matrix. These effects result from an inhibition by GABA of the evoked release of dopamine, since the reducing effects of bicuculline on iv-methyl-D-aspartate responses were not observed under the complete blockade of dopaminergic transmission by the D-1 and D-2 receptor antagonists. Further demonstrating 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-aspartate+D-serine, but also by 50 mu M N-methyl-D-aspartate. (C) 1997 IBRO. Published by Elsevier Science Ltd.
