Abstract

Interaction of γ-aminobutyric acid (GABA), pentobarbital and two neuroactive steroids on t-butylbicyclophosphorothionate ([³⁵S]TBPS) binding to GABA_A receptors in thalamus was studied during absence seizures. In control brain sections, the steroids alphaxalone and tetrahydrodeoxycorticosterone (at low 0.1–1 μM concentrations) increased [³⁵S]TBPS binding in thalamic relay nuclei. Both GABA and pentobarbital dose-dependently decreased [³⁵S]TBPS binding in these nuclei. A significant decrease in the ability of steroids to increase [³⁵S]TBPS binding in thalamic relay nuclei was observed during absence seizures induced by γ-hydroxybutyric acid (GHB). This loss of steroid effect on binding was 1) selective to steroids only as GABA and pentobarbital modulation of [³⁵S]TBPS binding in these nuclei did not change significantly and 2) not causally related to the generation of GHB-induced absence seizures as it was not observed at the onset of GHB-seizures but developed 30 min after the seizure-onset. We tested whether absence seizures were critical for the development of this loss of steroid effect on [³⁵S]TBPS binding in thalamic relay nuclei. The ability of the steroids to increase [³⁵S]TBPS binding in relay nuclei was preserved when GHB-seizures were blocked. When the duration of GHB-seizures was prolonged, the loss of steroid effect on [³⁵S]TBPS binding in thalamus persisted throughout the seizure-duration. These findings suggest that absence seizures cause a rapid loss of steroid effect on [³⁵S]TBPS binding to GABA_Areceptors in thalamic relay nuclei.