Modafinil Modulates GABA-activated Currents In Rat Hippocampal Pyramidal Neurons

Objective To study the effects of modafinil, a novel psychoactive drug, on the GABAA receptor-induced current in rat hippocampus pyramidal neurons with whole-cell patch- clamp recordings. The relationship among modafinil, IGABA and KATP channels were tested in order to discover the mechanism of curing epilepsy and analgesia underlying modafinil activity.Methods Whole-cell patch-clamp recordings were applied in cultured hippocampus pyramidal neurons. The control group was applicated GABA (0.1 mM) evoking an inward current (IGABA). The experimental groups were included two groups. In A group: modafinil was pre-perfused the neuron for 3 min in the external solution, then GABA (0.1 mM) was applied for 30 sec. In B group: after the neurons were cultured in the external solution with glibenclamide for 30 min, the protocol of the group A was repeated.Results In cultured hippocampus pyramidal neurons, the GABA-activated currents were blocked by bicuculline, a competitive antagonist of GABAA receptor. After pre- perfusion with modafinil (0.01, 0.1 and 1mM) for 3 min, IGABA was partly blocked in a dose-dependent manner. Pre-treating hippocampus neurons with glibenclamide for 30 min, modafinil-induced inhibition on IGABA was partly removed.Conclusion Modafinil is a new central noradrenergic receptor agonist in the treatment of narcolepsy. Unlike established psychostimulants, the effects of modafinil on GABA neurons are not straightforward,The protection of modafinil may be via modulating ATP sensitive potassium channel activation,at least in part mediated by KATP channel.