Steroid-inhibition of [3H]gamma-hydroxybutyric acid (GHB) binding in thalamic 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 interaction of 3alpha-hydroxy steroids, alphaxalone and tetrahydrodeoxycorticosterone (which are potent modulators of GABAA receptors) with GHB binding sites in rat brain cortical membranes. The steroids inhibited [3H]GHB binding in a dose-dependent fashion (IC50 approximately 1 microM). Neither bicuculline nor GABA altered the dose-response of steroids in the [3H]GHB assay, suggesting that there was no GABAA component involved in the steroid-inhibition of [3H]GHB binding. Also, non 3alpha-hydroxy steroids were inactive in displacing [3H]GHB. Because GHB-induced absence seizures evolve most readily from layers I-IV of frontoparietal cortex and thalamic relay nuclei, we determined if the interaction of steroids with GHB binding sites in layers I-IV of frontoparietal cortex and thalamic relay nuclei was altered during GHB-induced absence 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 regions tested. This increase in steroid-inhibition of [3H]GHB binding in 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 the enhancement in steroid-inhibition of [3H]GHB binding in thalamic relay nuclei observed during GHB-seizures was caused by absence seizures.