Jett D A, Kuhlmann A C, Farmer S J, Guilarte T R
Johns Hopkins University S.H.P.H., Department of Environmental Health Sciences, Baltimore, MD 21205, USA.
Pharmacol Biochem Behav. 1997 May-Jun;57(1-2):271-9. doi: 10.1016/s0091-3057(96)00350-4.
The neurobehavioral toxicity of developmental exposure to lead (Pb) was investigated by conducting tests of spatial learning in the Morris water maze. Female Long-Evans rats were exposed to 0 or 250 ppm Pb acetate in the diet beginning 10 days prior to breeding and continued throughout gestation and lactation. Pups were weaned onto the same diets as the dams at postnatal day 20 (PN20). Increased levels of Pb were detected in the hippocampus of the 250 ppm Pb acetate group relative to controls. The highest concentration of Pb measured in the hippocampus was at PN21 with decreasing levels at older ages. In the Morris Water Maze, a statistically significant (p < 0.03; female rats) or near significant (p < 0.07; male rats) increase in the time required to find the hidden platform (escape latency) was observed when Pb-treated rats were tested in a reference memory paradigm. This effect was only observed when rats were tested at PN21 and not at older ages. No significant effects of developmental Pb exposure were measured when rats were tested in a working memory paradigm of the Morris water maze at any age. These initial studies indicate an impairment of performance in the swim task in PN21 rats exposed to Pb during development. The age-dependent effect of Pb in this learning paradigm is consistent with previous studies in experimental animals and with the observation that children are more susceptible to Pb-induced cognitive deficits than adults. The Morris water maze may be useful for studying the effects of Pb on learning and memory, and their neurochemical basis.
通过在莫里斯水迷宫中进行空间学习测试，研究了发育期接触铅（Pb）的神经行为毒性。雌性Long-Evans大鼠在繁殖前10天开始，直至整个妊娠期和哺乳期，在饮食中接触0或250 ppm醋酸铅。幼崽在出生后第20天（PN20）断奶，与母鼠食用相同的饮食。与对照组相比，250 ppm醋酸铅组大鼠海马中的铅水平升高。海马中测得的最高铅浓度出现在PN21，随着年龄增长水平下降。在莫里斯水迷宫中，当对经铅处理的大鼠进行参考记忆范式测试时，观察到寻找隐藏平台所需时间（逃避潜伏期）有统计学意义的增加（p < 0.03；雌性大鼠）或接近显著增加（p < 0.07；雄性大鼠）。这种效应仅在大鼠于PN21进行测试时观察到，在较大年龄时未观察到。当在任何年龄对大鼠进行莫里斯水迷宫工作记忆范式测试时，未测量到发育期铅暴露的显著影响。这些初步研究表明，发育期接触铅的PN21大鼠在游泳任务中的表现受损。铅在这种学习范式中的年龄依赖性效应与先前在实验动物中的研究一致，也与儿童比成年人更容易受到铅诱导的认知缺陷影响的观察结果一致。莫里斯水迷宫可能有助于研究铅对学习和记忆的影响及其神经化学基础。
