Cagiano R, De Salvia M A, Renna G, Tortella E, Braghiroli D, Parenti C, Zanoli P, Baraldi M, Annau Z, Cuomo V
Institute of Pharmacology, University of Bari, Italy.
Neurotoxicol Teratol. 1990 Jan-Feb;12(1):23-8. doi: 10.1016/0892-0362(90)90108-o.
On day 15 of gestation, pregnant Sprague-Dawley rats were orally treated by gavage with 8 mg/kg of methyl mercury (MMC). At day 1 of postnatal life the levels of MMC in whole brain of exposed pups were found to be about 100 times higher than those of saline-exposed rats, while they were near to the control values at 21 days and practically normal at 60 days of age. Behavioral experiments showed that exposure to MMC in late gestation did not affect at any tested time (14, 21 and 60 days) locomotor activity or development of ultrasonic vocalization. An increased response to a challenge dose of amphetamine was, however, detected in MMC-exposed pups at day 14. This phenomenon was no longer evident at day 21 and 60 of age. In parallel, an increased density of dopamine receptors was found in the striatum at 14, but not at 21 and 60, days of age. From these data, we tentatively suggest that a high level of MMC induces a transient phenomenon of disuse-supersensitivity of the dopaminergic system. Moreover, further evidence that acute MMC exposure during prenatal life might induce permanent disturbances in learning and memory which could be partially related to a reduced functional activity of the glutamatergic system is provided.
在妊娠第15天,对怀孕的斯普拉格-道利大鼠经口灌胃给予8毫克/千克的甲基汞(MMC)。在出生后第1天,发现暴露幼崽全脑中的MMC水平比生理盐水暴露组大鼠高约100倍,而在21天时接近对照值,在60日龄时基本正常。行为实验表明,妊娠后期暴露于MMC在任何测试时间(14、21和60天)均不影响运动活动或超声发声的发育。然而,在出生后第14天,在暴露于MMC的幼崽中检测到对安非他明激发剂量的反应增强。这种现象在21日龄和60日龄时不再明显。同时,在14日龄时纹状体中多巴胺受体密度增加,但在21日龄和60日龄时没有增加。根据这些数据,我们初步认为高水平的MMC会诱发多巴胺能系统的一种暂时的废用超敏现象。此外,还提供了进一步的证据,即产前急性暴露于MMC可能会诱发学习和记忆的永久性障碍,这可能部分与谷氨酸能系统功能活动降低有关。