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

Curr Opin Pharmacol. 2007 Feb;7(1):77-85. doi: 10.1016/j.coph.2006.08.012. Epub 2006 Nov 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Conditioning, Psychological
  • Mitogen-Activated Protein Kinase 1 / physiology*
  • Mitogen-Activated Protein Kinase 3 / physiology
  • Neuronal Plasticity / physiology
  • Neurons / metabolism
  • Reward
  • Substance-Related Disorders*


  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3