Prenatal cocaine exposure adversely affects development of the primate cerebral cortex.

Abstract

This study was conducted to determine whether prenatal exposure to cocaine interferes with the development of the primate cerebral cortex. For this purpose, pregnant rhesus monkeys received cocaine orally (20 mg/kg/day in fruit or candy treats), twice a day from the 40th-102nd days of pregnancy (E40-E102), which is a period of corticogenesis in this species. The control group of pregnant animals received fruit or candy treats only. On E64 and E65, all animals received intravenous injections of [3H]thymidine. Monkeys were allowed to deliver at term. The offspring were sacrificed at age 2 months, and their brains were processed for histology and autoradiography. The analysis of cresyl violet-stained sections showed that prenatal treatment with cocaine significantly altered lamination of the primate cerebral cortex, in some cases completely blending distinction between individual layers. In addition, autoradiographic analysis revealed that in the control animals, [3H]thymidine labeling concentrated in cortical layers V and/or IV depending on the cytoarchitectonic area observed. In contrast, drug-treated animals displayed labeled cells in the white matter and cortical layer VI in addition to layers V and IV, suggesting inability of cortical cells to reach proper cortical layers. The number of labeled cells was also much lower in these animals. Finally, immunocytochemical studies with antisera directed toward glial fibrillary acidic protein showed that prenatal exposure to cocaine had dramatic effect on the glial fibers normally observed in the upper cortical layers. In many cortical regions of cocaine-treated animals, we observed practically no such fibers. This study demonstrates that cocaine administered during pregnancy can significantly affect the development of the primate cerebral cortex.