One signaling molecule that has been well studied in the two MSNs in the context of drug abuse is the protein kinase, ERK (extracellular signal related kinase). Acute or chronic exposure to cocaine induces phosphorylated ERK (pERK), the activated form of the protein, in the NAc and dStr in D1+ MSNs using D1-GFP and D2-GFP BAC transgenic reporter mice (Bertran-Gonzalez et al., 2008) and this response is mediated through D1 receptors (Valjent et al., 2000; Lu et al., 2006). This group also showed that pMSK-1 (phospho-MAP and stress activated kinase-1) and histone H3, both targets of pERK signaling, are robustly induced in pERK containing D1+ MSNs after acute cocaine exposure and modestly increased after chronic cocaine (Bertran-Gonzalez et al., 2008). pERK is also induced is response to chronic morphine, in particular, pERK is robustly induced in D1+ MSNs and modestly induced in D2+ MSNs in the NAc shell after withdrawal in response to the context-specific association with morphine (Borgkvist et al., 2008). The precise functional role of pERK in drug addiction remains to be determined. Pharmacological treatment with ERK inhibitors
