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 electrical 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 extracellular recordings. In the presence of the γ-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 non-phasic neurons in a dose-dependent manner. The reduction in the firing rate induced by baclofen was reversed by the selective GABA(B) antagonist, 2-hydroxy saclofen (2OH-saclofen), also in a dose-dependent manner. In non-phasic neurons, 2OH-saclofen significantly increased the firing rate and the effect was additive to the effect of picrotoxin. In phasic neurons, 2OH-saclofen 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 inhibition is not confined to SON neurons of male rats. The evidence indicates that activation of GABA(B) receptors inhibits electrical activity of SON neurons of both male and female rats and that GABA(B) receptors may play an important role in the inhibitory regulation of the electrical activity of SON neurons by GABA.