Calcium/calmodulin-dependent protein kinases (CaMKs) also regulate activation of ERK by drugs of abuse. KN93, which inhibits type II CaMK (CaMKII), prevents nicotine-mediated increases in p-ERK in mouse cortical neurons.37 Inhibition of CaMKI and its upstream activator CaMK kinase prevents NMDA-mediated increases in p-ERK in mouse hippocampal neurons.38 Given the role of NMDA receptors in drug-induced ERK activation, it is possible that CaMKI is also involved in the activation of ERK by drugs of abuse.
