GABA A receptor function in the γ-hydroxybutyrate model of generalized absence seizures
γ-Hydroxybutyric acid (GHB) produces absence-like seizures when given to animals. One of the distinguishing characteristics of experimental generalized absence seizures is that they are exacerbated by GABA A agonists. Therefore, the hypothesis that GHB-induced absence seizures result from an interac...
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Published in: | Neuropharmacology 1993-04, Vol.32 (4), p.401-409 |
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Main Authors: | , |
Format: | Article |
Language: | eng |
Subjects: | |
Online Access: | Get full text |
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Summary: | γ-Hydroxybutyric acid (GHB) produces absence-like seizures when given to animals. One of the distinguishing characteristics of experimental generalized absence seizures is that they are exacerbated by GABA
A agonists. Therefore, the hypothesis that GHB-induced absence seizures result from an interaction between GHB and the GABA
A receptor complex was tested. The effect of GHB on the function of various components of the GABA
A receptor complex in the cortex of the rat, was determined in a series of
in vitro experiments. Similar studies were carried out at various times following systemic administration of the prodrug of GHB, γ-butyrolactone (GBL) and changes in the GABA
A receptor were correlated with electrographic and behavioral changes.
γ-Hydroxybutyric acid had no effect on the binding of [
3H]muscimol, [
3H]flunitrazepam and [
35S]
t-butyl-bicyclophosphorothionate (TBPS) or on the uptake of
36Cl
− into synaptoneurosomes in the
in vitro studies. Nor were changes observed after the administration of GBL before the onesetof GHB-induced absence seizures. However, at the onset of GHB-induced spike wave discharge, there was a significant (
P < 0.04) decrease in the binding of [
35S]TBPS, associated with a significant decrease in muscimol-stimulated uptake of
36Cl
− with no other biochemical change. One minute after onset of GHB-induced absence seizure, a significant (
P < 0.05) increase in the binding of [
3H]muscimol was noted. Ten minutes later the decrease in muscimol-stimulated uptake of
36Cl
− had normalized, while the changes in binding of [
3H]muscimol and [
35S]TBPS persisted.
Because GABA
A function remained unchanged in the
in vitro studies, as well as prior to the onset of GHB-induced absence seizures in the
in vivo experiments, these studies do not support the hypothesis that GHB interacts directly with the GABA
A receptor complex to produce absence-like seizures. |
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ISSN: | 0028-3908 1873-7064 |