Modulation of Striatal Dopamine and Acetylcholine Release by Different Glutamate Receptors: Studies with in Vivo Microdialysis
There is evidence that striatal dopamine (DA) release is presynaptically modulated by a glutamatergic cortical input (see1,2,3) In the caudate of the push-pull cannulated cats4, as well as in striatal slice preparations in rats5, glutamate stimulates DA release. It was proposed4, that the DA stimulation produced by glutamate reflected direct axonal interactions between cortical glutamatergic and mesencephalic dopaminergic afferents, since the stimulating effect of L-glutamate was still observed in the presence of tetrodotoxin. This hypothesis has received some support from biochemical and histochemical studies showing direct intrastriatal axonal interactions between cortico-striatal projections and nigro-striatal DA terminals labeled with antibodies against the enzyme tyrosine hydroxylase5,6. However, the majority of the striatal afferents from the cortex and the substantia nigra make axodendritic synaptic contacts with striatal neurons7, giving a basis for polysynaptic loops including gamma-aminobutyric acid (GABA) and/or acetylcholine (ACh) neurons, by which cortical glutamate neurons could also modulate striatal dopamine release. There is now evidence that the excitatory action of glutamate is conveyed by multiple receptors, which have been pharmacologically differentiated and characterized, i.e. N-methyl-D-aspartate (NMDA)-, quisqualate- and kainate-receptors. All these receptors are found in the striatum (see8), but they appear located on different cells or associated with different synapses, thereby related to different functions. Indeed, it has been shown, that, in the cat caudate, cortically evoked monosynaptic excitatory postsynaptic potentials (EPSPs) are mediated by kainate or quisqualate, but not by NMDA receptors9. The present studies with in vivo microdialysis10 show that, in the striatum, in situ kainic acid (KA) stimulation increases DA, but decreases ACh. However, while NMDA is less potent that KA on DA release, it induces a dose-dependent increase in striatal AC release. Furthermore, it was found that cortical stimulation with either KA or NMDA produced a dose-dependent increase in striatal ACh release, but only a minor increase in striatal DA release.
KeywordsHigh Performance Liquid Chromatography Kainic Acid Striatal Dopamine Microdialysis Probe Perfusion Medium
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- 2.R. Romo, A. Cheramy, G. Godeheu, and J. Glowinski, In vivo presynaptic control of dopamine release in the cat caudate nucleus -I. Opposite changes in neuronal activity and release evoked from thalamic motor nuclei, Neuroscience 19: 1079 (1986).Google Scholar
- 8.C.W. Cotman, D.T. Monaghan, O.P. Ottersen and J. Storm-Mathisen, Anatomical organization of excitatory amino acid receptors and their pathways, TINS 10: 273 (1987).Google Scholar
- 10.U. Ungerstedt, M. Herrera-Marschitz, U. Jungnelius, L. Stâhle, L. Tossman and T. Zetterström, Dopamine synaptic mechanisms reflected in studies combining behavioural recordings and brain dialysis, in: “Advances in dopamine research, Advances in the Biosciences 37”, M. Kohsaka, T. Shomori, Y. Tsukada and G.N. Woodruff, eds, Pergamon Press, Oxford (1982).Google Scholar
- 11.K. Zilles, The cortex of the rat. A stereotaxic atlas, Springer, Berlin (1985).Google Scholar