Interaction among alfaxalone, pregnenolone sulfate, and two GABAA agonists on hippocampal slices.

Abstract

GABAA agonists do not respond to the same degree to allosteric modulators of the GABAA receptor complex such as benzodiazepines. We report there the effects of two steroids (alfaxalone and pregnenolone sulfate) on the inhibition induced by two GABAA agonists, 3-amino propane sulphonic acid (3-APS) and muscimol, on the extracellular evoked potentials obtained in CA1 of mice hippocampi. Alfaxalone (1 microM) potentiates the effects of both agonists, although incubation times longer than 15 minutes are required to potentiate the inhibitory effect of muscimol. Lower doses of pregnenolone sulfate at shorter incubation periods are able to inhibit the effects produced by single doses of 3-APS as compared to muscimol (15 microM during 5 min vs 30 microM during 5 min). Our results confirm the possibility that there might be differences in the interaction between GABAA agonists and modulatory steroids.