Distinct modifications by neurokinin1 (SR140333) and neurokinin2 (SR48968) tachykinin receptor antagonists of the N-methyl-D-aspartate-evoked release of acetylcholine in striosomes and matrix of the rat striatum

The effects of SR140333 and SR48968 (neurokinin(1) and neurokinin(2) tachykinin receptor antagonists, respectively) on the iv-methyl-D-aspartate-evoked release of [H-3]acetylcholine (previously formed from [H-3]choline) were investigated in striosome-enriched areas and in the matrix of the rat striatum using an in vitro microsuperfusion method. In both striatal compartments, SR140333 and SR48968 did not modify the 50 mu M N-methyl-D-aspartate-evoked release of [H-3]acetylcholine. However, in low concentrations, both SR140333 (0.1 mu M to 1 pM) and SR48968 (0.1 mu M to 0.1 nM) markedly enhanced the 1 mM N-methyl-D-aspartate (+10 mu M D-serine)-evoked release of [H-3]acetylcholine in striosome-enriched areas. These responses were dopamine-dependent since they were not observed any more following the local blockade of D-2 receptors by sulpiride or of dopamine synthesis by alpha-methyl-p-tyrosine. A dopamine-dependent disinhibitory effect (of lower amplitude) on the 1 mM N-methyl-D-aspartate (+10 mu M D-serine)-evoked release of [H-3]acetylcholine was also induced by SR48968 (0.1 mu M to 0.1 nM) (but not by SR140333) in the matrix. In addition, in the matrix. as shown only in the presence of alpha-methyl-p-tyrosine, both SR140333 and SR48968 reduced the 1 mM N-methyl-D-aspartate (+10 mu M D-serine)-evoked response and these non-dopamine-mediated inhibitory effects only occurred at the highest tested concentration (0.1 mu M) of the antagonists. Indicating the specificity of these responses, the effects of SR140333 were reproduced by RP67580, another neurokinin, receptor antagonist and, as expected from previous binding studies, corresponding SR140333 and SR48968 enantiomers were without effect. These results suggest that under potent stimulation of N-methyl-D-aspartate receptors, endogenously released substance P and neurokinin A (or related tachykinins) regulate differently the N-methyl-D-aspartate-evoked release of [H-3]acetylcholine in striosomes and in the matrix. The inhibitory effects of these tachykinins on the evoked release of [H-3]acetylcholine are mediated by dopamine. On the contrary, their facilitatory responses are only observed in the matrix under blockade of dopamine transmission. (C) 1998 IBRO. Published by Elsevier Science Ltd.