STEROID-INHIBITION OF [H-3]GAMMA-HYDROXYBUTYRIC ACID (GHB) BINDING INTHALAMIC RELAY NUCLEI INCREASES DURING ABSENCE SEIZURES

gamma-Hydroxybutyric acid (GHB), a naturally occurring analog of GABA, induces absence-like seizures in rats. We characterized the interacti on of 3 alpha-hydroxy steroids, alphaxalone and tetrahydrodeoxycortico sterone (which are potent modulators of GABA(A) receptors) with GHB bi nding sites in rat brain cortical membranes. The steroids inhibited [H -3]GHB binding in a dose-dependent fashion (IC50 similar to 1 mu M) Ne ither bicuculline nor GABA altered the dose-response of steroids in th e [H-3]GHB assay, suggesting that there was no GABA(A) component invol ved in the steroid-inhibition of [H-3]GHB binding. Also, non 3 alpha-h ydroxy steroids were inactive in displacing [H-3]GHB. Because GHB-indu ced absence seizures evolve most readily from layers I-IV of frontopar ietal cortex and thalamic relay nuclei, we determined if the interacti on of steroids with GHB binding sites in layers I-IV of frontoparietal cortex and thalamic relay nuclei was altered during GHB-induced absen ce seizures. We found that during GHB-seizures steroid-inhibition of [ 3H]GHB binding was increased selectively in thalamic relay nuclei but not in the layers I-IV of frontoparietal cortex or any other brain reg ions tested. This increase in steroid-inhibition of [H-3]GHB binding i n thalamus was apparent about 30 min after the onset of seizures, but not at the seizure-onset. As the seizures dissipated, the IC50 values for steroids rose to the pre-seizure level. These data suggest that th e enhancement in steroid-inhibition of [H-3]GHB binding in thalamic re lay nuclei observed during GHB-seizures was caused by absence seizures . (C) 1998 Elsevier Science B.V. All rights reserved.