Modulation of GABA-gated chloride ion influx in the brain by dehydroepiandrosterone and its metabolites

Both DHEA and GABA(A) receptor agonists are known to reduce anxiety. Since GABA(A) receptor agonists are generally thought to elicit their anxiolytic effects by facilitating neuronal uptake of chloride ion, we set out to evaluate whether DHEA elicits its anxiolytic effects by a similar mechanism. The results of the studies show an uneven distribution of basal and GABA-stimulated chloride uptake in different regions (cerebellum, pons-medulla, striatum, hippocampus, mid-brain, hypothalamus and cortex) of rat brain. Contrary to our expectations, however, both DHEA and DHEAS inhibited GABA-mediated chloride uptake with DHEAS being more potent than DHEA. On the other hand, Delta(4)- androstenedione, another DHEA metabolite, did not have any effect on chloride uptake in any region of the brain. In conclusion, the data presented here, therefore, suggest that DHEA and DHEAS may elicit anxiolysis through mechanisms independent of GABAA receptor-mediated facilitation of neuronal chloride uptake. (C) 1998 Academic Press.