GABA(B) receptor-mediated inhibition of spontaneous action potential discharge in rat supraoptic neurons in vitro

To elucidate the role of GABA(B) receptors in the regulation of the electri cal activity of magnocellular neurons of the supraoptic nucleus (SON), the effects of GABA(B) agonist and antagonist on the firing rate of spontaneous action potentials were studied in SON slice preparations of rats by extrac ellular recordings. In the presence of the gamma-amino butyric acid (GABA)- gated chloride channel blocker, picrotoxin, the selective GABA(B) agonist, baclofen, reduced the firing rate of action potentials in both phasic and n on-phasic neurons in a dose-dependent manner. The reduction in the firing r ate induced by baclofen was reversed by the selective GABA(B) antagonist, 2 -hydroxy saclofen (2OH-saclofen), also in a dose-dependent manner. In non-p hasic neurons, 2OH-saclofen significantly increased the firing rate and the effect was additive to the effect of picrotoxin. In phasic neurons, 2OH-sa clofen alone did not increase the firing rate, but it reversed suppression of the firing induced by increasing extracellular Ca2+ concentration to 2.1 mM. Baclofen also reduced the firing rate of non-phasic neurons of virgin and lactating female rats, indicating that the GABA(B) receptor-mediated in hibition is not confined to SON neurons of male rats. The evidence indicate s that activation of GABA(B) receptors inhibits electrical activity of SON neurons of both male and female rats and that GABA, receptors may play an i mportant role in the inhibitory regulation of the electrical activity of SO N neurons by GABA. (C) 1998 Elsevier Science B.V. All rights reserved.