ERK2: a logical AND gate critical for drug-induced plasticity? (2006)

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ERK  is another molecule activated by drugs of abuse and natural rewards. When blocked no addiction occurs.


Curr Opin Pharmacol. 2007 Feb;7(1):77-85. Epub 2006 Nov 7.

Girault JA, Valjent E, Caboche J, Hervé D.

Source

INSERM, UMR-S536, F-75005, Paris, France. girault@fer-a-moulin.inserm.fr

Abstract

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.