Steroid-inhibition of [3H]gamma-hydroxybutyric acid (GHB) binding in thalamic relay nuclei increases during absence seizures.
gamma-Hydroxybutyric acid (GHB), a naturally occurring analog of GABA, induces absence-like seizures in rats. We characterized the interaction of 3alpha-hydroxy steroids, alphaxalone and tetrahydrodeoxycorticosterone (which are potent modulators of GABAA receptors) with GHB binding sites in rat brain cortical membranes. The steroids inhibited [3H]GHB binding in a dose-dependent fashion (IC50 approximately 1 microM). Neither bicuculline nor GABA altered the dose-response of steroids in the [3H]GHB assay, suggesting that there was no GABAA component involved in the steroid-inhibition of [3H]GHB binding. Also, non 3alpha-hydroxy steroids were inactive in displacing [3H]GHB. Because GHB-induced absence seizures evolve most readily from layers I-IV of frontoparietal cortex and thalamic relay nuclei, we determined if the interaction of steroids with GHB binding sites in layers I-IV of frontoparietal cortex and thalamic relay nuclei was altered during GHB-induced absence seizures. We found that during GHB-seizures steroid-inhibition of [3H]GHB binding was increased selectively in thalamic relay nuclei but not in the layers I-IV of frontoparietal cortex or any other brain regions tested. This increase in steroid-inhibition of [3H]GHB binding in thalamus was apparent about 30 min after the onset of seizures, but not at the seizure-onset. As the seizures dissipated, the IC50 values for steroids rose to the pre-seizure level. These data suggest that the enhancement in steroid-inhibition of [3H]GHB binding in thalamic relay nuclei observed during GHB-seizures was caused by absence seizures.
Banerjee
P K
PK
Division of Neurology and The Brain and Behavior Program, Hospital for Sick Children, Department of Pediatrics, Faculty of Medicine, University of Toronto, 555 University Ave., Toronto, Ontario, Canada. pradeep.banerjee@mailhub.sickkids.on.ca
Liu
C C
CC
Snead
O C
OC
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology / Q000503:physiopathology; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D004832:Epilepsy, Absence / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D010296:Parietal Lobe / Q000737:chemistry / Q000166:cytology / Q000503:physiopathology; D011277:Pregnanediones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D013788:Thalamus / Q000737:chemistry / Q000166:cytology* / Q000503:physiopathology; D014316:Tritium; D015854:Up-Regulation / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000777:Anesthetics; D011277:Pregnanediones; D011963:Receptors, GABA-A; D014316:Tritium; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D005680:gamma-Aminobutyric Acid; C006477:alphaxalone