Enhancement of hippocampal acetylcholine release by the neurosteroid dehydroepiandrosterone sulfate: An in vivo microdialysis study

The effect of dehydroepiandrosterone sulfate (DHEAS) administered i.p. on the release of acetylcholine (ACh) from the hippocampus of anesthetized rats was examined using in vivo microdialysis. DHEAS significantly increased ACh release above the pre-treatment levels for all doses tested. The administration of 100 mg/kg significantly enhanced ACh release greater than 4-fold when compared to the saline-treated group 80 min following drug administration. This study is the first to demonstrate that the neurosteroid DHEAS, a negative allosteric modulator of the GABA(A) receptor, can enhance the release of ACh from neurons in the hippocampus.