This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous research indicates that testosterone enhances the survival of newly proliferated neurons in the adult hippocampus, and increased survival of hippocampal neurons may correlate with improved spatial memory. Therefore, adult neurogenesis may be the mechanism by which testosterone improves spatial working memory. We examined both performance on a working-reference memory version of the 8-arm radial maze (RAM) and 30-day hippocampal cell survival using castrated adult male rats. Subjects were injected with BrdU (200 mg/kg) to assess the survival of newly proliferated cells within the hippocampus. Beginning the following day, rats were run once daily for 29 days on the RAM. The number of both working memory errors (WME) and reference memory errors (RME) was scored. Each day prior to maze testing, rats were injected with either 0.5 mg of testosterone propionate (n = 10) or 0.1ml of oil vehicle (n = 10). BrdU-labeled cells were stained and scored on brain sections. Testosterone-injected subjects performed significantly fewer WMEs than did controls during the first ten days of testing. In contrast, testosterone had no significant effect on RMEs. This indicates that testosterone improves working memory but not reference memory. Surprisingly, testosterone had no effect on cell survival. This may have been because learning on the maze elevated neurogenesis levels in the control subjects. These results suggest that enhanced hippocampal cell survival may not be the mechanism by which testosterone improves spatial memory.
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