The effect of steroid sulfatase inhibition on learning and spatial memory

Steroid sulfatase inhibitors can enhance the concentration of the neuroster oid DHEAS in rat brain. Previous studies have demonstrated that the steroid sulfatase inhibitor (p-O-sulfamoyl)-N-tetradecanoyl tyramine (DU-14) could reverse scopolamine induced amnesia in rats in a passive avoidance memory paradigm. The intent of this study was to determine whether chronic pretrea tment with DU-14 could reverse scopolamine amnesia and/or enhance spacial m emory in the place, probe and cued versions of the Morris water maze (MWM). Rats were divided into four groups and administered IF for 15 days either DU-14 (30.0 mg/Kg) or corn oil (1.0 ml/Kg) vehicle. On training days animal s were administered either scopolamine (1.0 mg/Kg) or saline (1.0 ml/Kg). T he groups administered DU-14 displayed a significant enhancement in learnin g and spacial memory in the place version of the MWM, when compared to resp ective vehicle-scopolamine and vehicle-saline groups. In the probe version, the DU-14-saline group remained in the target quadrant of the maze signifi cantly longer than any of the other groups indicating enhanced retention. I n the cued version of the MWM, treatment with DU-14 did not significantly c hange escape latency suggesting that the steroid sulfatase inhibitor did no t alter motivation or locomotion. These results suggest that the chronic ad ministration of steroid sulfatase inhibitors enhance learning and spatial m emory in rats. (C) 2000 Published by Elsevier Science B.V. All rights reser ved.