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

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

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INSERM, UMR-S536, F-75005, Paris, France.


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.

[Indexed for MEDLINE]

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