CHANGES IN EXTRACELLULAR LEVELS OF GLUTAMATE AND ASPARTATE IN RAT SUBSTANTIA-NIGRA INDUCED BY DOPAMINE-RECEPTOR LIGANDS - IN-VIVO MICRODIALYSIS STUDIES

The microdialysis technique was utilized to study the local effects of D-1 and D-2 family type dopamine (DA) receptor (R) ligands on the in vivo release of endogenous glutamate (GLU) and aspartate (ASP) from ra t substantia nigra (SN). Addition to the dialysis perfusion solution o f either D-1-R and D-2-R agonists, such as SKF-38393 (50 and 100 mu M) and Quinpirole (5 and 10 mu M), resulted in dose-dependent increases in extracellular concentrations of GLU and ASP, respectively. The SKF- 38393 and Quinpirole-induced effects were reduced by SCH-23390 (0.5 mu M), a D-1-R antagonist, and by Spiperone (1.0 mu M), a D-2-R antagoni st, respectively. However, SCH-23390 and Spiperone did increase GLU an d ASP extracellular concentrations. Local infusion with Tetrodotoxin ( TTX) (1.0 mu M), a blocker of voltage-dependent Na+ channels, increase d basal extracellular levels of GLU. In addition, co-infusion of TTX a nd SKF-38393 evoked increases in extracellular GLU levels higher than those observed after SKF-38393 alone. Finally, chemical lesions of nig ral DA cells with 6-OH-DA. increased the basal extracellular levels of GLU. It is proposed that the release of GLU and ASP from SN may be re gulated by D-1- and D-2- receptors present in this basal ganglia struc ture. In addition, part of the D-1 receptors present in SN might be lo cated presynaptically on GLU-containing nerve endings.