Nonhuman primate model of the effect of prenatal cocaine exposure on cerebral cortical development.
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.
Department of Oral and Craniofacial Biological Sciences, University of Maryland, Baltimore 21201, USA. mlidow@umaryland.edu
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D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D003042:Cocaine / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008253:Macaca mulatta; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis; D019966:Substance-Related Disorders
D018341:Receptors, Adrenergic, alpha-2; D017447:Receptors, Dopamine D1; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine