title: 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.affiliation: Division of Neurology and the Brain and Behavior Program, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: P K
authors.initials: PK
authors.lastname: Banerjee
authors.forename: R W
authors.initials: RW
authors.lastname: Olsen
authors.forename: N J
authors.initials: NJ
authors.lastname: Tillakaratne
authors.forename: S
authors.initials: S
authors.lastname: Brailowsky
authors.forename: A J
authors.initials: AJ
authors.lastname: Tobin
authors.forename: O C
authors.initials: OC
authors.lastname: Snead
mesh_terms: D000200:Action Potentials; D000818:Animals; D001665:Binding Sites; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism*; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D006885:Hydroxybutyrates / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D011277:Pregnanediones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013462:Sulfur Radioisotopes; D013787:Thalamic Nuclei / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D006885:Hydroxybutyrates; D011277:Pregnanediones; D013462:Sulfur Radioisotopes; C111420:4-hydroxybutyric acid; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate; C006477:alphaxalone; D010424:Pentobarbital