Possible Role of the Extracellular Signal-Regulated Kinase (ERK) in Reward-Controlled Learning and Addiction

Emmanuel      Valjent; Denis      Herve; Jocelyne      Caboche; Jean-Antoine      Girault

Abstract

Drug addiction is characterized by loss of control over drug consumption, with compulsive drug seeking and taking, despite obvious adverse consequences. It is a chronic brain disorder since the increased risk of relapse to active drug use remains high even after years of abstinence. Current research attempts to identify the cellular and molecular basis for the neuronal modifications underlying these complex behavioural alterations. Strong evidence indicates that the extracellular signal-regulated kinase (ERK) pathway is a conserved intracellular signalling module, critical for various types of learning and synaptic plasticity. Recent results show that drugs of abuse activate this pathway in the brain regions important for reward-controlled learning and addiction. Moreover, pharmacological and genetic approaches support a role of the ERK pathway in some of the long-term effects of addictive drugs. We suggest that drug-induced stimulation of the ERK pathway by dopamine in specific brain areas may be an exaggeration of its normal role in learning controlled by reward, and may contribute significantly to the acquisition of specific behaviours characteristic of drug addiction.

Keywords: extracellular signal-Regulated kinase, erk, reward-controlled learning, addiction, brain disorder, learning and synaptic plasticity, erk pathway, drug addiction