Chunk #21 — Extracellular Signal-Regulated Kinases — ERK in Addiction-Related Behaviors — Differential Effects of ERK1 and ERK2 in Responses to Drugs of Abuse
Current MEK inhibitors do not distinguish between ERK1 and ERK2. However, studies with ERK1 knockout mice suggest that ERK1 and ERK2 play different roles in some responses to addictive drugs. ERK1 knockout mice show increased ERK2-mediated signaling.57 These mice also show enhanced development of cocaine-induced psychomotor sensitization58 and much greater cocaine-58 and morphine-induced CPP than wild-type mice.57 In addition, place conditioning for cocaine increases phosphorylation of ERK2 but not ERK1 in the rat NAc.52 These results suggest that ERK2 might be the more important ERK isoform in mediating drug-induced CPP and sensitization to cocaine.
