The release of [H-3]gamma-aminobutyric acid ([H-3]GABA) continuously formed from [H-3]glutamine has been measured with a push-pull cannula implanted in the substantia nigra of the rat anesthetized with ketamine. Consistent with the high density of GABA terminals coming from both the striato-pallido-nigral afferents, and from GABA nigrofugal neurons, our results showed that a large amount of [H-3]GABA was spontaneously released in the reticulata, about 4 times higher than in the compacta. In the absence of calcium the spontaneous [H-3]GABA release was reduced (-30%), as well as the K+-induced release of [H-3]GABA (-66%). Bicuculline (10(-4) M) did not affect the K+-evoked release of [H-3]GABA, suggesting that autoreceptors on GABA afferent fibers, are distinct from the GABA(A) subtype. Partial lesions of striato- and pallido-nigral GABA neurons with kainic acid (1.2-mu-g) decrease by 40% the glutamic acid decarboxylase (GAD) activity in the ipsilateral SN without decreasing the spontaneous release of [H-3]GABA; even following extensive lesions with kainic acid (2.5-mu-g), GAD activity (-72%) and spontaneous [H-3]GABA release (-83%) were not completely abolished. These results suggest that a non-negligible contribution of GABA nigral neurons accounts for the spontaneous GABA release measured in the substantia nigra. This is further supported by the decrease (-20%), and the increase (+40%) of [H-3]GABA release produced by the local application of glycine (10(-6) M), and bicuculline (10(-4) M), which respectively, inhibits and activates the nigral neuron activity. The contribution of nigral GABA neurons to the amount of [H-3]GABA release from the substantia nigra, is likely linked to their high spontaneous firing rate.
