Treatment with dehydroepiandrosterone sulfate increases NMDA receptors in hippocampus and cortex

Our aim was to investigate if the memory-enhancing effects reported for dehydroepiandrosterone sulfate in rodents could be mediated through modulation of NMDA receptors. Using autoradiography we studied the effect of dehydroepiandrosterone sulfate, administered for 5 days (30 mg/kg, i.p. twice a day), on NMDA binding sites labelled with [3H]dizocilpine ([3H]MK801) in rat brain. Dehydroepiandrosterone sulfate treatment significantly increased the [3H]MK801 binding sites in hippocampal areas (field CA1, CA3, dentate gyrus lateral blade and medial blade) and in cortex layer IV as compared to the control group. These results demonstrate for the first time the ability of dehydroepiandrosterone sulfate to increase the number of NMDA binding sites in rat brain, an action that could be of interest for therapeutic application.