ERK2: a logical AND gate critical for drug-induced plasticity?

Jean‐antoine Girault (1) , Emmanuel Valjent (1) , Jocelyne Caboche (2) , Denis Hervé (1)

1 Transduction du Signal et Plasticite Dans Le Systeme Nerveux
2 NPA - Neurobiologie des processus adaptatifs

Drug addiction results in part from the distortion of dopamine-controlled plasticity, and extracellular signal-regulated kinase (ERK) plays an important role in the underlying molecular mechanisms of this process. ERK is activated by drugs of abuse in a subset of neurons in reward-related brain regions. This activation, necessary for the expression of immediate early genes, depends upon dopamine D1 and glutamate receptors. Blockade of ERK activation prevents long-lasting behavioral changes, including psychomotor sensitization and conditioned place preference. It also interferes with drug craving and drug-associated memory reconsolidation. By contrast, ERK1 mutation enhances the effects of morphine and cocaine. We suggest that the ERK2 pathway acts as a logical AND gate, permissive for plasticity, in neurons on which dopamine-mediated reward signals and glutamate-mediated contextual information converge.

Mots clés: protein kinase; ERK; dopamine; glutamate; striatum; signal transduction; nucleus accumbens; drugs of abuse; addiction; cocaine; reward; plasticity; model

Domaines: Neurosciences [q-bio.NC]

Jean‐antoine Girault, Emmanuel Valjent, Jocelyne Caboche, Denis Hervé. ERK2: a logical AND gate critical for drug-induced plasticity?: ERK2 and drug-induced plasticity. Current Opinion in Pharmacology, 2007, 7 (1), pp.77-85. ⟨10.1016/j.coph.2006.08.012⟩. ⟨inserm-00128883⟩