REVERSAL OF SCOPOLAMINE-INDUCED AMNESIA IN RATS BY THE STEROID SULFATASE INHIBITOR ESTRONE-3-O-SULFAMATE

The intent of the study was to determine whether altering the metaboli sm of neurosteroids via blockade of the enzyme, steroid sulfatase, cou ld enhance retention test performance in rats. The steroid sulfatase i nhibitor estrone-3-O-sulfamate (EMATE) was administered alone and in c ombination with the neurosteroid dehydroepiandrosterone sulfate (DHEAS ) to rats which were then tested for the reversal of scopolamine induc ed amnesia. EMATE enhanced the reversal of amnesia by DHEAS as measure d by a passive avoidance test. When administered without DHEAS, as a s ingle acute dose, EMATE had no effect. When administered without DHEAS over 10 consecutive days, however, EMATE significantly improved reten tion. These results suggest that steroid sulfatase inhibition can pote ntiate the memory enhancing properties of DHEAS. The study also sugges ts that increasing the levels of endogenous sulfated neurosteroids via the inhibition of steroid sulfatase activity may enhance learning and /or memory function.