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 metabolism of neurosteroids via blockade of the enzyme, steroid sulfatase, could enhance retention test performance in rats. The steroid sulfatase inhibitor estrone-3-O-sulfamate (EMATE) was administered alone and in combination with the neurosteroid dehydroepiandrosterone sulfate (DHEAS) to rats which were then tested for the reversal of scopolamine induced amnesia. EMATE enhanced the reversal of amnesia by DHEAS as measured by a passive avoidance test. When administered without DHEAS, as a single acute dose, EMATE had no effect. When administered without DHEAS over 10 consecutive days, however, EMATE significantly improved retention. These results suggest that steroid sulfatase inhibition can potentiate the memory enhancing properties of DHEAS. The study also suggests that increasing the levels of endogenous sulfated neurosteroids via the inhibition of steroid sulfatase activity may enhance learning and/or memory function.
Li
P K
PK
Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
Rhodes
M E
ME
Jagannathan
S
S
Johnson
D A
DA
D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001192:Arylsulfatases / Q000037:antagonists & inhibitors*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004970:Estrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D012601:Scopolamine / Q000037:antagonists & inhibitors*; D043266:Steryl-Sulfatase
D004791:Enzyme Inhibitors; C088768:estrone-3-O-sulfamate; D004970:Estrone; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D012601:Scopolamine; D001192:Arylsulfatases; D043266:Steryl-Sulfatase