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

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Abstract

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.

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Acknowledgments

This work was supported in part by the Program for New Century Excellent Talents in University, the National Basic Research Program of China (973 Program, 2007CB512302 and 2003CB515400), the National High Technology Research and Development Program of China (863 Program, 2006AA02Z4D1), and the Natural Science Foundation of China (Nos. 30570576 and 30670713).

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Correspondence to Lin Lu.

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Haifeng Zhai and Yanqin Li contributed equally to this paper.

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Zhai, H., Li, Y., Wang, X. et al. Drug-induced Alterations in the Extracellular Signal-regulated Kinase (ERK) Signalling Pathway: Implications for Reinforcement and Reinstatement. Cell Mol Neurobiol 28, 157–172 (2008). https://doi.org/10.1007/s10571-007-9240-3

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