ON THE RELEASE OF GLUTAMATE AND ASPARTATE IN THE BASAL GANGLIA OF THERAT - INTERACTIONS WITH MONOAMINES AND NEUROPEPTIDES

Using highly sensitive analytical procedures, glutamate (Glu), asparta te (Asp) and several putative neurotransmitters and metabolites can be monitored simultaneously in the extracellular space of neostriatum, s ubstantia nigra and cerebral cortex of the rat by in vivo microdialysi s. Glu and Asp are found at sub-micromolar concentrations in all inves tigated brain regions. In order to ascertain their neuronal origin, we have extensively studied the sensitivity of extracellular Glu and Asp levels to: (i) K+-depolarization, (ii) Na+-channel blockade, (iii) re moval of extracellular Ca2+, (iv) depletion of presynaptic vesicles, a nd (v) integrity of neuronal pathways. The relevance of these criteria for several neurotransmitters monitored simultaneously or in parallel experiments has also been examined. The functional interactions among different neuronal pathways in the basal ganglia are studied by using selective pharmacological treatments, administered systemically, or l ocally via intracerebral injections or the microdialysis perfusion med ium. Immunohistochemical evidence for the existence of Glu and/or Asp neuronal pathways in the basal ganglia of the rat is presented, discus sing especially new findings indicating the existence of a Glu-indepen dent Asp system, intrinsic to the neostriatum of the rat. The clinical relevance of these interactions is discussed, focusing on the implica tions for the treatment of neurodegenerative disorders affecting the b asal ganglia. (C) 1997 Elsevier Science Ltd.