Glutamate receptor activation induces carrier mediated release of endogenous GABA from rat striatal slices

The regulation of striatonigral and striatopallidal GABAergic neurons by glutamatergic afférents is thought to play a critical role in normal basal ganglia function. Here we report that in striatal slices about 17% of K⁺-induced endogenous GABA release was Ca²⁺-independent and this could be blocked by a GABA transport inhibitor. Activation of N-methyl-D-aspartate (NMDA)- and quisqualate-sensitive receptors induced endogenous GABA efflux only in the presence of a GABA transaminase inhibitor; this efflux was inhibited by 60-80% with a GABA transport inhibiter. NMDA-induced GABA release was blocked by phencyclidine, Mg²⁺ and COS 19755. Quisqualate-induced GABA release was blocked completely by a combination of the metabotropic antagonist, L-AP3 and CNQX, a non-NMDA receptor antagonist. These data indicate that excitatory amino acid agonistsinduced GABA release is distinct from that induced by high K⁺ depolarization.