RAT SUBSTANTIA-NIGRA PARS RETICULATA NEURONS ARE TONICALLY INHIBITED VIA GABA(A), BUT NOT GABA(B), RECEPTORS IN-VITRO

Extracellular single unit recordings were made from substantia nigra p ars reticulata (SNr) neurones in slices of rat brain. Cells fired spon taneous action potentials at 11.4 +/- 0.8 Hz. The GABA, receptor agoni st isoguvacine (1-10 mu M) reduced firing rate in a concentration-depe ndent manner [50% of maximal inhibition (IC50) with 3.2 mu M], as did the GABA(B) agonist baclofen (0.3-10 mu M; IC50 1.4 mu M). The GABA(A) antagonist bicuculline (30 mu M) not only blocked the action of isogu vacine, but also increased the basal firing rate to 187.5 +/- 12.6% of control. The GABA(B) antagonist CGP 55845A (0.1 mu M), while blocking the inhibitory action of baclofen, was without effect on spontaneous firing rate, as was strychnine (10 mu M), the antagonist of glycine an d taurine, and also Met-enkephalin (10 mu M) Tiagabine (50 mu M), the blocker of GABA uptake, caused an inhibition of firing which could be reversed with bicuculline (30 mu M) but not CGP 55845A (1 mu M) We con clude that the firing rate of SNr neurones is under tonic inhibition b y GABA in vitro, which can be relieved by antagonists of GABA(A), but not GABA(B) receptors, and enhanced by blockade of GABA reuptake. The source of this GABA tone is likely to be from recurrent axon collatera ls of SNr neurones themselves.