Effect of cocaine on cell proliferation in the cerebral wall of monkey fetuses

This study examined the effect of cocaine on cell proliferation in the fetal monkey cerebral wall. Pregnant monkeys received cocaine daily (10 mg/kg, orally, in fruit treats, at 07.00 h and 19.00 h) beginning on the 40th day of pregnancy (E40). The control animals received fruit treats only. One set of monkeys was used to examine the state of cell proliferation in the fetal cerebral wall at peak cocaine levels. These animals were injected with [(3)H]thymidine intravenously on E73, 1.5 h after the morning drug or placebo administration. Another set of monkeys was used to determine the state of cell proliferation after cocaine concentration declined to ineffective levels. These animals were injected with [(3)H]thymidine on the same day of pregnancy 10 h after the treatment. Cesarean sections were performed 40 min after the radioisotope injection. The right hemispheres were processed for autoradiography. The left hemispheres were used for biochemical analysis of the radioisotope incorporation into DNA. The third set of monkeys was used to determine whether chronic cocaine treatment extends the timing of neocortical neuronogenesis. These monkeys received their final cocaine treatment on E102 (the last day of normal neocortical neuronogenesis) and were injected with [(3)H]thymidine 24 h later. On E113, the fetal brains were processed for emulsion autoradiography. We found a significant decrease in the density of [(3)H]thymidine-labeled cells and in the levels of this radioisotope incorporation into DNA in the fetal cerebral wall 1.5 h after cocaine administration. In contrast, 10 h after cocaine administration we detected a significantly elevated density of radiolabeled cells, and abnormally high levels of [(3)H]thymidine incorporation into DNA. This suggests that chronic intermittent administration of cocaine results in significant periodic fluctuations in cell production within the fetal cortical proliferative zones. We detected no cocaine-induced extension in neocortical neuronogenesis.