Abstract
Interaction of γ-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 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 GABAAreceptors in thalamic relay nuclei.
Footnotes
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Send reprint requests to: Dr. Pradeep K. Banerjee, Department of Neurology/The Epilepsy Research Program, Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada.
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↵1 This work was supported by the Brain and Behavior Program, Division of Neurology, Hospital for Sick Children, Toronto; National Institutes of Health Grants NS 17117 (O.C.S.), NS 28772 (R.W.O.) and NS 22256 (A.J.T.).
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↵2 Deceased May 28, 1998: to whom this work is dedicated.
- Abbreviations:
- GHB
- γ-Hydroxybutyric acid
- GABA
- γ-aminobutyric acid
- THDOC
- tetrahydrodeoxycorticosterone
- TBPS
- t-butylbicyclophosphorothionate
- GBL
- γ-butyrolactone
- EEG
- electroencephalogram
- ROD
- relative optical density
- Received March 26, 1998.
- Accepted June 16, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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