Cocaine inhibition of neuronal differentiation in NGF-induced PC12 cells is independent of ras signaling

In utero exposure to cocaine may result in altered neuronal development. Ou r previous studies demonstrated cocaine inhibits neurite outgrowth in NGF-i nduced PC12 cells through dopamine, by activation of D-1 receptors. This st udy examined where cocaine interferes in the NGF signaling cascade. GSras1 cells that inducibly express activated forms of Pas upon treatment with dex amethasone were used. Morphological differentiation was quantified by count ing cells bearing neurite-like processes after 72 h exposure to either dexa methasone or NGF alone, or with cocaine, dopamine or SKF-38393. Cocaine, do pamine, and the D-1 agonist inhibited neurite-like process outgrowth in bot h dexamethasone and NGF-induced GSras1 cells. GAP-43 expression, used as a measure for biochemical differentiation was severely diminished in NGF and dexamethasone-induced GSras1 cells treated with cocaine. These results sugg est that cocaine, dopamine and activation of D-1 receptors affect the NGF s ignaling downstream, independent of ras expression, leading to altered neur onal differentiation. (C) 2000 ISDN. Published by Elsevier Science Ltd. All rights reserved.