Anticonvulsant activity of muscimol and gamma-aminobutyric acid against pyridoxal phosphate-induced epileptic seizures

Abstract

The intracerebroventricular injection of pyridoxal phosphate (PLP, 0.125-1.25 mumol/rat) causes epileptic seizures (4 min leads to 1 min) that are preventable or reversible by GABA (1 mumol/rat), by muscimol (0.025 mumol/rat), or by diazepam (1.75 mumol/rat). At the peak of PLP-induced convulsions, the activities of GAD and GABA-T in 14 regions of rat brain remained unaltered, whereas the concentrations of PLP remained elevated. The PLP-induced convulsion was blocked by DABA (10 mumol/rat) but was not altered by beta-alanine (50 mumol/rat). The previous in vitro studies have shown that PLP increases the uptake of [3H]GABA into synaptosomes and inhibits the binding of [3H]GABA to synaptic membranes. These data suggest that PLP-induced convulsion is due to reduced availability of GABA to its recognition sites, rather than to alteration in the activity of GABA metabolizing enzymes, or unavailability of PLP as a coenzyme for GAD and GABA-T. Since the duration of PLP-induced epileptic seizures is short and can be prevented by GABA agonists, PLP may be used as a tool to study the nature of GABA-mediated neuroinhibition and the properties of GABA receptor sites.