Absence seizures decrease steroid modulation of t-[35S]butylbicyclophosphorothionate binding in thalamic relay nuclei.

Abstract

Interaction of gamma-aminobutyric acid (GABA), pentobarbital and two neuroactive steroids on t-butylbicyclophosphorothionate ([35S]TBPS) binding to GABAA receptors in thalamus was studied during absence seizures. In control brain sections, the steroids alphaxalone and tetrahydrodeoxycorticosterone (at low 0.1-1 microM 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 gamma-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 GABAA receptors in thalamic relay nuclei.

• Authors: P K Banerjee, R W Olsen, N J Tillakaratne, S Brailowsky, A J Tobin, O C Snead 3rd
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 287 Issue 2 Pg. 766-72 (Nov 1998) ISSN: 0022-3565 [Print] United States
• PMID: 9808708 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Hydroxybutyrates
• Pregnanediones
• Sulfur Radioisotopes
• 4-hydroxybutyric acid
• Desoxycorticosterone
• tetrahydrodeoxycorticosterone
• gamma-Aminobutyric Acid
• tert-butylbicyclophosphorothionate
• alphaxalone
• Pentobarbital

Topics

• Action Potentials
• Animals
• Binding Sites
• Bridged Bicyclo Compounds, Heterocyclic (metabolism)
• Desoxycorticosterone (analogs & derivatives, pharmacology)
• Epilepsy, Absence (chemically induced, metabolism, physiopathology)
• Hydroxybutyrates (pharmacology)
• Male
• Pentobarbital (pharmacology)
• Pregnanediones (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Sulfur Radioisotopes
• Thalamic Nuclei (drug effects, metabolism)
• gamma-Aminobutyric Acid (pharmacology)