RT Journal Article
SR Electronic
T1 Absence Seizures Decrease Steroid Modulation of <em>t</em>-[<sup>35</sup>S]Butylbicyclophosphorothionate Binding in  Thalamic Relay Nuclei
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 766
OP 772
VO 287
IS 2
A1 Pradeep K. Banerjee
A1 Richard W. Olsen
A1 Niranjala J. K. Tillakaratne
A1 Simon Brailowsky
A1 Allan J. Tobin
A1 O. Carter Snead III
YR 1998
UL http://jpet.aspetjournals.org/content/287/2/766.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics