INVOLVEMENT OF THE GLUTAMATERGIC METABOTROPIC RECEPTORS IN THE REGULATION OF GLUTAMATE UPTAKE AND EXTRACELLULAR EXCITATORY AMINO-ACID LEVELS IN THE STRIATUM OF CHLORAL HYDRATE-ANESTHETIZED RATS

The microdialysis technique was used to assess in vivo the putative fu nctional role of metabotropic excitatory amino acid receptors in regul ating extracellular levels of the excitatory amino acids glutamate and aspartate in the striatum of chloral hydrate-anesthetized rats. Addit ion of the metabotropic glutamate receptor antagonist (+)-alpha-methyl -4-carboxyphenylglycine (MCPG) (10(-3) or 4 x 10(-3) M) in the dialysi s probe did not modify the basal extracellular levels of glutamate and aspartate but induced a significant dose-dependent decrease in the KC l-elicited elevation of glutamate and aspartate extracellular levels. The effect of MCPG on glutamate extracellular concentration under K+ s timulation was reduced by the simultaneous superfusion of the metabotr opic glutamate receptor agonist (2S,3S,4S)-alpha-(carboxycyclopropyl)g lycine (L-CCG) (10(-3) M) which had no significant effect when tested alone. In contrast, L-CCG alone significantly potentiated the KCl-elic ited elevation of aspartate extracellular concentrations but failed to modify the MCPG effect on this amino acid concentration. In a paralle l series of experiments, high-affinity glutamate uptake was measured e x vivo 20 min after an in vivo injection of 10 pmol of MCPG in the str iatum. MCPG was found unable to modify the glutamate uptake rate. In v itro, MCPG (1-1000 mu M) again had no effect on glutamate transport ra te. These data suggest that metabotropic excitatory amino acid recepto rs (1) may act to increase the extracellular levels of glutamate and a spartate under depolarizing conditions, and (2) may not have a major r ole in the regulation of high affinity glutamate uptake under basal co nditions. In addition, it can be assumed that the control of glutamate and aspartate extracellular levels may involve different metabotropic receptors.