Effect of GABAmimetics on electrocorticographic spike discharges induced by guanidinoethanesulfonic acid (amidino-taurine) in the rat

Abstract

The effect of guanidinoethanesulfonic acid (GES) on rat electrocorticograms (ECoG) and the effects of gamma-aminobutyric acid (GABA) and GABA-agonists on the ECoG changes induced by GES were studied. Sporadic spike discharges began 2-5 min after 1 mumol GES/10 microliters on filter paper was applied to the pia mater of the left sensorimotor cortex; spike discharges extended to the opposite cerebral hemisphere 60 min after the onset of the ipsilateral spike discharges. The spike discharges with a frequency of 5-10 spikes/min lasted until the end of the 4 hour recording. The induced spike discharges were suppressed when the original GES soaked filter paper was replaced by one containing GES (1 mumol) supplement combined with taurine (1 mumol/10 microliters). GABA (1 mumol) and its receptor agonist, muscimol (10 nmol) and (3R)-(-)-4-amino-3-hydroxybutyric acid (1 mumol) also suppressed the GES-induced spike discharges when applied topically. Diazepam (DZP) (10 mg/kg) suppressed the GES-induced spike discharges 10 min after i.p. injection, but phenobarbital (20 mg/kg) increased the frequency and voltage of spike discharges 100 min following subcutaneous administration. Intraperitoneal injection of either valproate (200 mg/kg) or phenytoin (25 mg/kg), after the completion of the spike discharges, showed no effect. These findings suggest that neurotransmission or neuromodulatory effects of taurine participate in GES-induced seizure activity, and that GABAA and DZP receptors may play a role in the mechanism that suppresses GES-induced seizures.