GLUTAMATE-RECEPTOR ACTIVATION INDUCES CARRIER-MEDIATED RELEASE OF ENDOGENOUS GABA FROM RAT STRIATAL SLICES

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