Primates exposed to cocaine in utero display reduced density and number ofcerebral cortical neurons

This study examined the effects of cocaine use during the second trimester of pregnancy on cerebral neocortical volume and density, and total number o f neocortical neurons and glia in offspring. We also evaluated the extent o f postnatal recovery of cytoarchitectural abnormalities previously observed in the neocortex of two-month-old primates born from cocaine-treated mothe rs (Lidow [1995] Synapse 21:332-334). Pregnant monkeys received cocaine ora lly (20 mg/kg/day) from the 40th to 102nd days of pregnancy (embryonic day [E]40 - E102). On E64 and E65, the animals were injected with [H-3]thymidin e. Cerebral hemispheres of the offspring were examined at three years of ag e. We found a reduction in the neocortical volume and density and total num ber of neocortical neurons. The observed reduction in neuronal number withi n the neocortex was not accounted for by the increase in the number of neur ons in the white matter of cocaine-exposed animals, because the number of t hese "extra" neurons was equal to only half that of missing neurons. We det ected no significant changes in the number of neocortical glia. The cytoarc hitectural abnormalities in the neocortex of prenatally cocaine-exposed thr ee-year-old monkeys closely resembled previously described neocortical abno rmalities in similarly exposed two-month-old animals: the neocortex lacked a discernible lamination; the majority of the cells labeled by [H-3]thymidi ne injected during neocortical neuronogenesis did not reach their proper po sition within the cortical plate. Therefore postnatal maturation is not ass ociated with significant improvement in neocortical organization in primate s prenatally exposed to cocaine. There was, however, a postnatal recovery o f low glial fibrillary acidic protein (GFAP) immunoreactivity previously ob served in 2-month-old cocaine-exposed animals. (C) 2001 Wiley-Liss, Inc.