Cocaine affects cerebral neocortical cytoarchitecture in primates only if administered during neocortical neuronogenesis.

Previously, we demonstrated that chronic exposure of fetal monkeys to cocaine could result in development of the neocortex with significant cytoarchitectonic abnormalities [Synapse, 21 (1995) 435-444]. In the present study, we examined the developmental time-frame within which neocortical cytoarchitecture is susceptible to modifications by prenatal cocaine exposure. For this purpose, we assessed the integrity of cortical lamination and the position, density, and total number of occipital cortical neurons in 2-month-old monkeys which were prenatally exposed to chronic cocaine treatment either prior to the period of neocortical neuronogenesis, during the period of neocortical neuronogenesis, or after the period of neocortical neuronogenesis. We found that cocaine can interfere with the neocortical laminar organization and induce a reduction in the density and number of neocortical neurons only if it is administered at the time of neocortical neuronogenesis. During this window of vulnerability, an abnormal neocortex is generated as long as cocaine exposure is maintained, with corticogenesis becoming normal as soon as the administration of this drug is discontinued.