Testosterone has been shown to have dose-dependent effects on spatial memory in males, but the effects of aging upon this relationship remain unclear. Additionally, the mechanism by which testosterone regulates memory is unknown, but may involve changes in brain-derived neurotrophic factor (BDNF) within specific brain regions. We tested the effects of age and testosterone on spatial memory among male rats using two spatial memory tasks: an object-location memory task (OLMT) and the radial-arm maze (RAM). Castration had minimal effect on performance on the RAM, but young rats (2 months) performed significantly fewer working memory errors than aged rats (20 months), and aged rats performed significantly fewer reference memory errors. Both age and castration impaired performance on the OLMT, with only the young rats with intact gonads successfully performing the task. Subsequent experiments involved daily injections of either drug vehicle or one of four doses of testosterone propionate (0.125, 0.250, 0.500, and 1.00 mg/rat) given to castrated aged males. On the RAM, a low physiological dose (0.125 mg) and high doses (0.500-1.000 mg) of testosterone improved working memory, while an intermediate dose (0.250 mg) did not. On the OLMT, only the 0.250 mg T group showed a significant increase in exploration ratios from the exposure trials to the testing trials, indicating that this group remembered the position of the objects. Brain tissue (prefrontal cortex, hippocampus, and striatum) was collected from all subjects to assay BDNF. We found no evidence that testosterone influenced BDNF, indicating that it is unlikely that testosterone regulates spatial memory through changes in BDNF levels.

中文翻译：

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睾酮替代导致老年雄性大鼠空间记忆的剂量依赖性改善

睾酮已被证明对男性的空间记忆具有剂量依赖性影响，但衰老对这种关系的影响尚不清楚。此外，睾酮调节记忆的机制尚不清楚，但可能涉及特定大脑区域内脑源性神经营养因子 (BDNF) 的变化。我们使用两种空间记忆任务测试了年龄和睾酮对雄性大鼠空间记忆的影响：物体位置记忆任务 (OLMT) 和径向臂迷宫 (RAM)。阉割对 RAM 的性能影响很小，但年轻大鼠（2 个月）的工作记忆错误明显少于老年大鼠（20 个月），老年大鼠的参考记忆错误明显更少。年龄和阉割都会影响 OLMT 的表现，只有具有完整性腺的幼鼠成功地完成了这项任务。随后的实验包括每天注射药物载体或四种剂量的丙酸睾酮（0.125、0.250、0.500 和 1.00 毫克/大鼠）之一给阉割的老年男性。在 RAM 中，低生理剂量（0.125 毫克）和高剂量（0.500-1.000 毫克）睾酮改善了工作记忆，而中等剂量（0.250 毫克）则没有。在 OLMT 上，只有 0.250 mg T 组显示从暴露试验到测试试验的探索率显着增加，表明该组记住了物体的位置。从所有受试者收集脑组织（前额叶皮层、海马和纹状体）以测定 BDNF。我们没有发现睾酮影响 BDNF 的证据，