Neuroactive steroids exacerbate gamma-hydroxybutyric acid-induced absence seizures in rats.

Abstract

Certain naturally-occurring steroid metabolites and their synthetic analogs (neuroactive steroids) allosterically enhance GABA(A) receptor function and possess potent anticonvulsant properties. In the present study, the effect of two synthetic neuroactive steroids, alphaxalone (5alpha-pregnane 3alpha-ol-11, 20-dione) and tetrahydrodeoxycorticosterone was studied in a rat model of generalized absence seizures induced by gamma-hydroxybutyric acid. Both steroids dose-dependently exacerbated gamma-hydroxybutyric acid-induced absence seizures upon systemic administration and after focal administration into thalamic ventrobasal nucleus. However, alphaxalone and tetrahydrodeoxycorticosterone failed to potentiate gamma-hydroxybutyric acid-induced absence seizures when injected into thalamic reticular nucleus. In all the doses of steroids tested in thalamic reticular nucleus, the duration of gamma-hydroxybutyric acid-seizures was neither prolonged nor shortened. This nonresponsiveness of thalamic reticular nucleus to neuroactive steroids in modulating absence seizures may have arisen due to the molecular heterogeneity of GABA(A) receptor subunits within the thalamus.

• Authors: P K Banerjee, O C Snead 3rd
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 359 Issue 1 Pg. 41-8 (Oct 16 1998) ISSN: 0014-2999 [Print] Netherlands
• PMID: 9831291 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics
• Hydroxybutyrates
• Pregnanediones
• 4-hydroxybutyric acid
• Desoxycorticosterone
• tetrahydrodeoxycorticosterone
• alphaxalone

Topics

• Anesthetics (pharmacology)
• Animals
• Desoxycorticosterone (analogs & derivatives, pharmacology)
• Epilepsy, Absence (chemically induced, physiopathology)
• Hydroxybutyrates
• Male
• Pregnanediones (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Thalamic Nuclei (drug effects)