EVIDENCE FOR NEURONAL ORIGIN AND METABOTROPIC RECEPTOR-MEDIATED REGULATION OF EXTRACELLULAR GLUTAMATE AND ASPARTATE IN RAT STRIATUM IN-VIVOFOLLOWING ELECTRICAL-STIMULATION OF THE PREFRONTAL CORTEX

Extracellular levels of glutamate (Glu) and aspartate (Asp) were measu red at 5-s intervals in the striatum of chloral hydrate-anesthetized r ats by using microdialysis coupled to an automated assay system based on capillary electrophoresis with laser-induced fluorescence, Applicat ion of a single 10-s train of depolarizing pulses to the prefrontal co rtex caused a rapid increase in Glu and Asp concentrations (200-300% o f basal value), which returned to basal level within 60 s, The stimula ted rise in Glu and Asp concentrations was blocked completely by 2 mu M tetrodotoxin or depletion of extracellular Ca2+, suggesting a neuron al origin of the Glu and Asp, Infusion of the Glu transport inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (200 mu M) increased resting Glu and Asp levels by 300-500% without altering electrically stimulat ed changes in Glu and Asp concentration, Stimulated Glu and Asp concen tration changes were suppressed by 91 and 73%, respectively, by the me tabotropic Glu receptor agonist (1S,3R)-1-aminocyclopentane-trans-1 ,3 -dicarboxylate (200 mu M). This effect was blocked by the metabotropic Glu receptor antagonist (RS) -alpha-methylcarboxyphenylglycine (MCPG; 200 mu M). MCPG alone produced no effect on electrically stimulated c hanges in Glu and Asp levels; however, in the presence of L-trans-pyrr olidine-2,4-dicarboxylic acid, MCPG produced a five-to sixfold increas e in stimulated overflow, Based on these results, it is concluded that release of Glu and Asp from corticostriatal neurons can be inhibited by activation of metabotropic Glu autoreceptors, which may be an impor tant determinant of excitatory transmission at striatal synapses.