他莫昔芬对雌性大鼠学习记忆能力的影响

目的：探讨腹腔注射选择性雌激素受体调节剂他莫昔芬（tamoxifen，TC）对雌性大鼠学习记忆能力的影响。方法：将60只成年雌性SD大鼠随机分为空白对照组、溶剂对照组、TC2．5mg·kg^-1组、TC5．0mg·kg^-1组、TC10．0mg·kg^-1组5组，采用Morris水迷宫、跳台及八臂迷宫等行为学实验检测TC对雌性SD大鼠空间辨别学习记忆能力、被动回避条件反射能力及主动学习记忆能力的影响。结果：与溶剂对照组相比，3周后，TC各剂量组被动回避条件反射能力明显下降（P〈0．05），表现为跳台实验中的逃避潜伏期显著减少，错误反应次数明显增加。6周后，TC各剂量组大鼠的空间辨别学习记忆能力、被动回避条件反射能力及主动学习记忆能力均明显下降（P〈0．05），表现为Morris实验定位航行的潜伏期增加，目的象限的停留时间减少，第一次到达平台的时间延长；跳台实验中逃避潜伏期显著减少，错误反应次数明显增加；八臂迷宫实验中主动学习过程中总路程明显延长，典型性错误次数显著增加。结论：雌性SD大鼠腹腔注射TC6周后，其学习记忆能力随着TC剂量的增加而降低，TC对雌性SD大鼠的学习记忆能力具有明显的损伤作用。

Effects of Tamoxifen on Learning and Memory in Female Rats

Objective： To investigate the effects of tamoxifen on learning and memory abilities in female rats after intraperitoneal injection （ip） of the selective estrogen receptor modulator. Methods： Adult female Sprague-Dawley （SD）rats （n=60）were randomly assigned into 5 groups （control group, vehicle group, 2.5 mg·kg^-1 of TC group, 5.0 mg·kg^-1 of TC group and 10.0 mg·kg^-1 of TC group）. Morris water maze test, step-down test and 8-arm maze task were used to test the effects of tamoxifen on spatial learning and memory ability, passive avoidance conditioned reflex ability and active learning and memory ability in female SD rats, respectively. Results： Compared with vehicle group, passive avoidance conditioned reflex ability of the rats after ip of TC for three weeks was significantly decreased （P〈0.05）. After six weeks of drug treatment, the discriminability on spatial learning and memory ability, passive avoidance conditioned reflex ability and active learning and memory ability were all significantly reduced in these female SD rats （P〈0.05）. Conclusion： The results suggested that after tamoxifen treatment for six weeks, the learning and memory abilities in female SD rats were decreased dose-dependently, and that tamoxifen could cause substantial learning and memory deficits in female SD rats.