Fugger H N, Cunningham S G, Rissman E F, Foster T C
Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, 22903, USA.
Horm Behav. 1998 Oct;34(2):163-70. doi: 10.1006/hbeh.1998.1475.
This study investigated the role of the estrogen receptor alpha (ERalpha) in mediating performance on a spatial discrimination task, the Morris water maze. Spatial discrimination on this water escape task was examined in eight groups of gonadectomized mice. Male and female wild-type (WT) and littermate mice lacking functional copies of the ERalpha gene (ERalphaKO), were treated with estradiol benzoate (EB) or sesame oil vehicle. Subjects were trained on the water escape task over a 4-day period (four trials per block, three blocks per day). Latency to find the hidden platform was measured. Only female WT mice treated with EB failed to learn this spatial discrimination task. All males, WT and ERalphaKO treated with EB or oil exhibited decreased latencies across blocks of trials, WT females treated with oil, and ERalphaKO females, regardless of treatment, learned the spatial discrimination task. In order to eliminate motivational or sensory-motor impairments as a factor in describing the poor spatial discrimination performance of WT females treated with EB, the cue version of the water maze task was employed. Results from the cue phase of the task indicate that EB and oil-treated WT females exhibited a similar decrease in escape latencies across blocks of trials, indicating good cue discrimination performance. Taken together, the results indicate that ERalpha activation impairs acquisition of spatial discrimination of the water escape task, but not cue discrimination, in female mice. Because ligand-bound ERalpha appears to operate differently in male and female mice we hypothesize that the ability of ERalpha to affect learning is organized during development.
本研究调查了雌激素受体α（ERα）在介导空间辨别任务（莫里斯水迷宫）表现中的作用。在八组去势小鼠中检测了该水迷宫逃避任务中的空间辨别能力。雄性和雌性野生型（WT）小鼠以及缺乏ERα基因功能拷贝的同窝小鼠（ERαKO），分别用苯甲酸雌二醇（EB）或芝麻油载体进行处理。实验对象在4天时间内接受水迷宫逃避任务训练（每个时段进行4次试验，每天3个时段）。记录找到隐藏平台的潜伏期。只有接受EB处理的雌性WT小鼠未能学会这个空间辨别任务。所有接受EB或油处理的雄性WT和ERαKO小鼠在各试验时段的潜伏期均缩短，接受油处理的WT雌性小鼠以及ERαKO雌性小鼠，无论接受何种处理，都学会了空间辨别任务。为了排除动机或感觉运动障碍作为描述接受EB处理的WT雌性小鼠空间辨别能力差的一个因素，采用了水迷宫任务的线索版本。任务线索阶段的结果表明，接受EB和油处理的WT雌性小鼠在各试验时段的逃避潜伏期均有类似程度的缩短，表明其线索辨别能力良好。综合来看，结果表明ERα激活会损害雌性小鼠对水迷宫逃避任务的空间辨别能力的习得，但不影响线索辨别能力。由于配体结合的ERα在雄性和雌性小鼠中的作用方式似乎不同，我们推测ERα影响学习的能力是在发育过程中形成的。
