Lidow M S
Department of Oral and Craniofacial Biological Sciences, University of Maryland, Baltimore 21201, USA.
Ann N Y Acad Sci. 1998 Jun 21;846:182-93.
To investigate the effects of prenatal cocaine exposure on the corticogenesis in primates we developed a monkey model in which pregnant animals received 10 mg/kg cocaine orally twice a day from the 40th to the 102nd day of pregnancy. The animals gave birth at term, and brains of the 2-month and 1.5-year-old infants were examined. Examination revealed the structural abnormalities throughout the cerebral cortex that would be expected from modulation of the nonselectively diffusing circulation-derived monoamines. They include: (1) reduction in the number of cortical cells, which most likely reflects abnormal cell proliferation; (2) inappropriate positioning of cortical neurons, which resulted from alterations in migration of cortical cells; and (3) altered glial morphology. The structural alterations were accompanied by abnormalities in animal temperament reminiscent of those seen in human infants of drug-abusing mothers. As predicted by the morphologic studies, we found that cocaine treatment produced significant changes in the levels of monoamines and their receptors in all laminae of the frontal, parietal, temporal, and occipital regions of the fetal cerebral wall. This indicates that cocaine abuse by pregnant human mothers may affect the global levels of monoamines in the fetal brain and, in doing so, interfere with a broad range of developmental events regulated by these chemicals.
为了研究孕期接触可卡因对灵长类动物皮质发生的影响，我们建立了一个猴子模型，在该模型中，怀孕的动物在孕期第40天至102天期间每天口服两次10毫克/千克的可卡因。这些动物足月分娩，对2个月大和1.5岁大的幼猴的大脑进行了检查。检查发现整个大脑皮层存在结构异常，这些异常是由非选择性扩散的循环衍生单胺的调节所导致的。它们包括：（1）皮质细胞数量减少，这很可能反映了细胞增殖异常；（2）皮质神经元定位不当，这是由皮质细胞迁移改变导致的；（3）神经胶质形态改变。这些结构改变伴随着动物性情异常，类似于在滥用药物母亲所生人类婴儿中看到的情况。正如形态学研究所预测的，我们发现可卡因处理使胎儿脑壁额叶、顶叶、颞叶和枕叶所有层中的单胺及其受体水平发生了显著变化。这表明怀孕的人类母亲滥用可卡因可能会影响胎儿大脑中整体单胺水平，进而干扰由这些化学物质调节的广泛发育事件。
