Cocaine regulates ezrin-radixin-moesin proteins and RhoA signaling in the nucleus accumbens.

The ezrin-radixin-moesin (ERM) proteins are a family of widely distributed membrane-associated proteins and have been implicated not only in cell-shape determination but also in signaling pathway. The nucleus accumbens (NAcc) is an important neuronal substrate mediating the effects of drugs of abuse. However, it has not been determined yet how ERM proteins are regulated in this site by drugs of abuse. Here we show in rat that the phosphorylation levels of ERM protein are dose- and time-dependently decreased in the NAcc by a single injection of cocaine (15 or 30 mg/kg i.p.). Further, we show that the amount of active RhoA, a small GTPase protein, is significantly reduced in the NAcc by cocaine, while the phosphorylation levels of ERM protein are also decreased by bilateral microinjections in this site of the Rho kinase inhibitors. Together, these results suggest that cocaine reduces phosphorylated ERM levels in the NAcc by making downregulation of RhoA-Rho kinase signaling, which may importantly contribute to initiate synaptic changes in this site leading to drug addiction.