GABA terminal autoreceptors in the pars compacta and in the pars reticulata of the rat substantia nigra are GABA B

Abstract

The depolarization-evoked release of γ-aminobutyric acid (GABA) and its modulation mediated by autoreceptors were studied in superfused synaptosomes prepared from the pars compacta and from the pars reticulata of the rat substantia nigra. The release of [ 3H]GABA evoked by 9 mM KCl was almost totally calcium-dependent in both nigral subregions. In the presence of SK&F 89976A (N-(4,4-diphenyl-3-butenyl)nipecotic acid), a GABA uptake inhibitor added to minimize carrier-mediated homoexchange, GABA (0.3–10 μM) inhibited, in a concentration-dependent way, the K +-evoked overflow of [ 3H]GABA from both pars compacta and pars reticulata synaptosomes. Similarly to GABA, (−)-baclofen (0.3–10 μM) reduced the [ 3H]GABA overflow, being roughly equipotent to GABA in both nigral subregions. The (+) enantiomer of baclofen was ineffective. The overflow of [ 3H]GABA was not consistently affected by muscimol in either the pars compacta or the pars reticulata. The effects of GABA were bicuculline- and picrotoxin-insensitive. However, the inhibition by GABA of the [ 3H]GABA overflow was antagonized by phaclofen. It is concluded that (a) GABA autoreceptors are sited on GABAergic nerve endings in both the pars compacta and pars reticulata of the rat substantia nigra; (b) these autoreceptors belong to the GABA B type.