In VivoElectrochemical Studies of the Dynamic Effects of Locally Applied Excitatory Amino Acids in the Striatum of the Anesthetized Rat

The actions of locally applied excitatory amino acids (EAAs) on dopamine nerve terminals in the striatum of the urethane-anesthetized rat were investigated. Rapid (5 Hz) in vivo electrochemical recording was used to measure the amplitude and duration of dopamine (DA) overflow elicited by the local application of glutamate, N-methyl-D- aspartate (NMDA), kainate, quisqualate, quinolinate and DL- alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid. EAAs were pressure ejected into the striatum via a pipette positioned 300 +/- 30 mum away from the electrochemical working electrode. Brief (5s) applications of the EAA agonists directly elicited DA-like electrochemical signals with amplitudes averaging about 2 microM. In some instances, putative increases in ascorbic acid-like signals were detected. Repeated applications of glutamate agonists in the same brain site resulted in diminished electrochemical responses, compared to the complete reproducibility seen after repeated applications of 120 mM potassium. Low doses of NMDA (10 mM barrel conc), which did not cause a detectable increase in the electrochemical baseline signal, significantly potentiated (50%) potassium-evoked DA overflow. These results indicate that low levels of endogenously released glutamate may modulate overflow when DA nerve terminals are depolarized, while higher concentrations of glutamate may directly elicit increases in extracellular levels of DA and/or ascorbic acid.