Ziegler Dana R, Gallagher Michela
Department Psychological and Brain Sciences, John Hopkins University, Baltimore, MD 21218, USA.
Brain Res. 2005 Aug 9;1052(2):163-73. doi: 10.1016/j.brainres.2005.06.006.
Previous studies have shown that estrogen influences diverse aspects of neuronal function and morphology and modulates acquisition of various memory tasks in young adult female rodents. It is not clear whether estrogen is critical for optimal memory function in middle-aged female animals, i.e. when cyclicity gradually declines. We trained young adult (5 months) and older (10 months) female Long-Evans rats on a win-shift (delay) 12-arm radial maze (7 arms blocked pre-delay). Rats were preoperatively trained to criterion (< or =2 errors/trial for 3 days) with no delay then with a 60 s delay. All rats were ovariectomized when the age groups were 9 (Y) and 14 months (MA), respectively. Following recovery and retraining to criterion, each rat underwent consecutive treatment cycles with vehicle (Oil) or 17-beta-estradiol benzoate (E). Each 6-day acute treatment cycle, modeled after protocols previously shown to induce morphological and electrophysiological plasticity in the hippocampus at 24-48 h after estrogen injection, consisted of two consecutive daily injections of 10 microg E or Oil (0.1 ml subcutaneously) on Days 1-2 (Oil-Oil or E-E), testing on Days 3-4 at 60 s or 6 h delays, with Days 5-6 comprising of washout days. Each rat received a total of 4 treatment cycles, alternating between Oil and E cycles, in counterbalanced order. Estrogen treatment had no effect in either age group on pre-delay or post-delay errors at either 60 s or 6 h delays. The data indicate that the cyclic estrogen replacement regimen does not influence spatial memory function in young or middle-aged animals in the hippocampal-dependent appetitive radial maze task. Discussion of these unexpected results includes consideration of important experimental design factors that differ between our study and some previous reports, such as the extensive training and task experience our subject received prior to testing for estrogen effects.
先前的研究表明，雌激素会影响神经元功能和形态的多个方面，并调节年轻成年雌性啮齿动物各种记忆任务的习得。目前尚不清楚雌激素对于中年雌性动物的最佳记忆功能是否至关重要，即在周期性逐渐下降时。我们在一个赢-转换（延迟）12臂放射状迷宫（7臂在延迟前被阻挡）上训练年轻成年（5个月）和年长（10个月）的雌性Long-Evans大鼠。大鼠在术前接受训练直至达到标准（连续3天每次试验错误≤2次），开始时无延迟，然后有60秒延迟。当年龄组分别为9个月（年轻组）和14个月（中年组）时，所有大鼠均接受卵巢切除术。恢复并重新训练至标准后，每只大鼠接受用赋形剂（油）或苯甲酸17-β-雌二醇（E）进行的连续治疗周期。每个为期6天的急性治疗周期，仿照先前显示在雌激素注射后24 - 48小时可诱导海马体形态和电生理可塑性的方案，包括在第1 - 2天连续两天每天皮下注射10微克E或油（0.1毫升）（油-油或E-E），在第3 - 4天以60秒或6小时延迟进行测试，第5 - 6天为洗脱期。每只大鼠总共接受4个治疗周期，以平衡的顺序在油周期和E周期之间交替。雌激素治疗在任何一个年龄组中，对于60秒或6小时延迟时的延迟前或延迟后错误均无影响。数据表明，在海马体依赖性的奖赏性放射状迷宫任务中，周期性雌激素替代方案不会影响年轻或中年动物的空间记忆功能。对这些意外结果的讨论包括考虑我们的研究与一些先前报告之间不同的重要实验设计因素，例如我们的实验对象在测试雌激素作用之前所接受的广泛训练和任务经验。
