The effect of steroid sulfatase inhibition on learning and spatial memory.
Steroid sulfatase inhibitors can enhance the concentration of the neurosteroid 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 pretreatment with DU-14 could reverse scopolamine amnesia and/or enhance spacial memory in the place, probe and cued versions of the Morris water maze (MWM). Rats were divided into four groups and administered IP for 15 days either DU-14 (30.0 mg/Kg) or corn oil (1.0 ml/Kg) vehicle. On training days animals were administered either scopolamine (1.0 mg/Kg) or saline (1.0 ml/Kg). The groups administered DU-14 displayed a significant enhancement in learning and spacial memory in the place version of the MWM, when compared to respective vehicle-scopolamine and vehicle-saline groups. In the probe version, the DU-14-saline group remained in the target quadrant of the maze significantly longer than any of the other groups indicating enhanced retention. In the cued version of the MWM, treatment with DU-14 did not significantly change escape latency suggesting that the steroid sulfatase inhibitor did not alter motivation or locomotion. These results suggest that the chronic administration of steroid sulfatase inhibitors enhance learning and spatial memory in rats.
Johnson
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DA
Division of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Duquesne University, 15282, Pittsburgh, PA, USA. johnsond@duq.edu
Wu
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T
Li
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P
Maher
T J
TJ
D000647:Amnesia / Q000139:chemically induced; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects*; D008297:Male; D018727:Muscarinic Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine; D014439:Tyramine / Q000031:analogs & derivatives* / Q000494:pharmacology
C103321:4-O-(sulfamoyl)-N-tetradecanoyltyramine; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D012601:Scopolamine; D014439:Tyramine