Cellular and Molecular Neurobiology

, Volume 28, Issue 2, pp 157–172

Drug-induced Alterations in the Extracellular Signal-regulated Kinase (ERK) Signalling Pathway: Implications for Reinforcement and Reinstatement

Review Paper

DOI: 10.1007/s10571-007-9240-3

Cite this article as:
Zhai, H., Li, Y., Wang, X. et al. Cell Mol Neurobiol (2008) 28: 157. doi:10.1007/s10571-007-9240-3


Drug addiction, characterized by high rates of relapse, is recognized as a kind of neuroadaptive disorder. Since the extracellular signal-regulated kinase (ERK) pathway is critical to neuroplasticity in the adult brain, understanding the role this pathway plays is important for understanding the molecular mechanism underlying drug addiction and relapse. Here, we review previous literatures that focus on the effects of exposure to cocaine, amphetamine, Δ9-tetrahydrocannabinol (THC), nicotine, morphine, and alcohol on ERK signaling in the mesocorticolimbic dopamine system; these alterations of ERK signaling have been thought to contribute to the drug’s rewarding effects and to the long-term maladaptation induced by drug abuse. We then discuss the possible upstreams of the ERK signaling pathway activated by exposure of drugs of abuse and the environmental cues previously paired with drugs. Finally, we argue that since ERK activation is a key molecular process in reinstatement of conditioned place preference and drug self-administration, the pharmacological manipulation of the ERK pathway is a potential treatment strategy for drug addiction.


Addiction Neuroplasticity Reward Relapse Dopamine Glutamate Contextual cues 

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Department of Neuropharmacology, National Institute on Drug Dependence Peking UniversityHai Dian DistrictChina

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