Cohn J, Cory-Slechta D A
Department of Environmental Medicine, University of Rochester School of Medicine & Dentistry, NY 14642.
Neurotoxicol Teratol. 1994 Sep-Oct;16(5):455-65. doi: 10.1016/0892-0362(94)90123-6.
Several studies now suggest that Pb exposure disrupts NMDA receptor complex function, findings which may have implications for understanding the basis of Pb-induced learning impairments. To further evaluate this possibility, the behavioral properties of the glutamate agonist NMDA were compared in rats that had been chronically exposed to 0, 50, or 250 ppm Pb acetate in drinking water from weaning. Acute administration of NMDA (20-50 mg/kg IP) decreased accuracy in both the repeated acquisition (RA) and performance (P) components of this multiple schedule with a selective effect on the learning component in the second half of the session. Analyses of error patterns revealed that the disruption of RA accuracy derived from initial perseverative errors followed by errors of skipping forward and backwards in the 3-member response sequence. Response rates in both RA and P were suppressed by NMDA. Pb-exposure potentiated the accuracy-impairing effects of NMDA by further increasing the frequencies of these error classes, and likewise potentiated the rate-suppressing effects of NMDA. These findings add further support to the possible involvement of Pb with the NMDA receptor complex.
目前多项研究表明，铅暴露会破坏N-甲基-D-天冬氨酸（NMDA）受体复合物的功能，这些发现可能有助于理解铅诱发学习障碍的基础。为了进一步评估这种可能性，研究人员比较了从断奶起就长期饮用含0、50或250 ppm醋酸铅饮用水的大鼠体内谷氨酸激动剂NMDA的行为特性。急性注射NMDA（20 - 50 mg/kg，腹腔注射）会降低这种多重实验安排中重复习得（RA）和操作（P）部分的准确性，对实验后半段的学习部分有选择性影响。对错误模式的分析表明，RA准确性的破坏源于最初的持续性错误，随后是在三元反应序列中向前和向后跳过的错误。NMDA抑制了RA和P中的反应率。铅暴露通过进一步增加这些错误类型的频率，增强了NMDA对准确性的损害作用，同样也增强了NMDA对反应率的抑制作用。这些发现进一步支持了铅可能与NMDA受体复合物有关的观点。
