The ezrin–radixin–moesin (ERM) proteins have been implicated not only in cell-shape determination but also in cellular signaling pathway. We have previously shown that cocaine decreases phosphorylation levels of these proteins in the nucleus accumbens (NAcc), an important brain area mediating addictive behaviors. Here we further revealed that the phosphorylation levels of ERM were decreased in the NAcc core, but not in the shell, by a single injection of amphetamine (AMPH) (2 mg/kg, IP). When lithium (100 mg/kg, IP) was co-administered with AMPH, the decreases of phosphorylation levels for ERM by AMPH were recovered back to basal levels in the NAcc core. Together, these results suggest that psychomotor stimulants like AMPH regulate phosphorylation levels of ERM in the NAcc core and lithium-involved signaling pathway has a regulatory role in the opposite direction in this site.