Vol. 287, Issue 2, 766-772, November 1998

Absence Seizures Decrease Steroid Modulation of t-[³⁵S]Butylbicyclophosphorothionate Binding in Thalamic Relay Nuclei¹

Pradeep K. Banerjee , Richard W. Olsen , Niranjala J. K. Tillakaratne, Simon Brailowsky² , Allan J. Tobin and O. Carter Snead, III

Division of Neurology and the Brain and Behavior Program, Hospital for Sick Children, Toronto (P.K.B., O.C.S.), Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 1X8, Canada (P.K.B., O.C.S.); Departments of Pharmacology (R.W.O.), Physiological Sciences (A.J.T., N.J.K.T.) and Neurology (A.J.T.), the Molecular Biology Institute and the Brain Research Institute, University of California, Los Angeles, California (R.W.O., A.J.T.) and Neurociencias, Instituto de Fisiologia Celular, U.N.A.M., Mexico D.F. 04510, Mexico (S.B.)

Interaction of -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 -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_A receptors in thalamic relay nuclei.