Inhibitory effects of cocaine on NGF-induced neuronal differentiation: incomplete reversibility after a critical time period.

We extend our findings showing dose-dependent cocaine inhibition of differentiation in NGF-stimulated PC-12 cells without affecting cell viability by demonstrating that neurite extension is severely limited after 24 h, maximal effect is reached at 36 h and recovery is only partial. Cocaine metabolites lack these effects. A similar process may occur following human prenatal exposure, perhaps through cocaine-induced changes in gene expression or other intracellular signalling events.