Extracellular signal-regulated protein kinases 1 and 2 activation by addictive drugs: a signal toward pathological adaptation
Language: 
English
Short Title: 
Extracellular signal-regulated protein kinases 1 and 2 activation by addictive drugs
Abstract: 

Addiction is a chronic and relapsing psychiatric disorder that is thought to occur in vulnerable individuals. Synaptic plasticity evoked by drugs of abuse in the so-called neuronal circuits of reward has been proposed to underlie behavioral adaptations that characterize addiction. By increasing dopamine in the striatum, addictive drugs alter the balance of dopamine and glutamate signals converging onto striatal medium-sized spiny neurons (MSNs) and activate intracellular events involved in long-term behavioral alterations. Our laboratory contributed to the identification of salient molecular changes induced by administration of addictive drugs to rodents. We pioneered the observation that a common feature of addictive drugs is to activate, by a double tyrosine/threonine phosphorylation, the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the striatum, which control a plethora of substrates, some of them being critically involved in cocaine-mediated molecular and behavioral adaptations. Herein, we review how the interplay between dopamine and glutamate signaling controls cocaine-induced ERK1/2 activation in MSNs. We emphasize the key role of N-methyl-D-aspartate receptor potentiation by D1 receptor to trigger ERK1/2 activation and its subsequent nuclear translocation where it modulates both epigenetic and genetic processes engaged by cocaine. We discuss how cocaine-induced long-term synaptic and structural plasticity of MSNs, as well as behavioral adaptations, are influenced by ERK1/2-controlled targets. We conclude that a better knowledge of molecular mechanisms underlying ERK1/2 activation by drugs of abuse and/or its role in long-term neuronal plasticity in the striatum may provide a new route for therapeutic treatment in addiction.

Author(s): 
Pascoli, Vincent
Cahill, Emma
Bellivier, Frank
Caboche, Jocelyne
Vanhoutte, Peter
Item Type: 
Journal Article
Publication Title: 
Biological Psychiatry
Journal Abbreviation: 
Biol. Psychiatry
Publication Date: 
12/15/2014
Publication Year: 
2014
Pages: 
917-926
Volume: 
76
Issue: 
12
ISSN: 
1873-2402
DOI: 
10.1016/j.biopsych.2014.04.005
Library Catalog: 
PubMed
Extra: 
PMID: 24844603

Turabian/Chicago Citation

Vincent Pascoli, Emma Cahill, Frank Bellivier, Jocelyne Caboche and Peter Vanhoutte. 12/15/2014. "Extracellular signal-regulated protein kinases 1 and 2 activation by addictive drugs: a signal toward pathological adaptation." Biological Psychiatry 76: 12: 917-926. 10.1016/j.biopsych.2014.04.005.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.biopsych.2014.04.005 | issn = 1873-2402 | volume = 76 | pages = 917-926 | last = Pascoli | first = Vincent | coauthors = Cahill, Emma, Bellivier, Frank, Caboche, Jocelyne, Vanhoutte, Peter | title = Extracellular signal-regulated protein kinases 1 and 2 activation by addictive drugs: a signal toward pathological adaptation | journal = Biological Psychiatry | date = 12/15/2014 | pmid = | pmc = }} </ref>