ENHANCED PLASMA DHEAS, BRAIN ACETYLCHOLINE AND MEMORY MEDIATED BY STEROID SULFATASE INHIBITION

Steroid sulfatase inhibitors can alter the metabolism of neurosteroids which modulate brain function. Administration of the non-steroidal st eroid sulfatase inhibitor (p-O-sulfamoyl)-N-tetradecanoyl tyramine (DU -14) to rats for 15 days increased plasma dehydroepiandrosterone sulfa te (DHEAS) concentrations by 88.2%, decreased plasma dehydroepiandrost erone (DHEA) concentrations by 84.6%, increased hippocampal acetylchol ine (ACh) release determined via in vivo microdialysis by almost 3-fol d, and produced a significant blockade of scopolamine-induced amnesia as measured by a passive avoidance test. These results suggest DHEAS r ather than DHEA enhances brain cholinergic function and that steroid s ulfatase inhibition may become an important tool for enhancing neurona l functions, such as memory, mediated by excitatory neurosteroids. (C) 1997 Elsevier Science B.V.