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Emergence of context‐associated GluR 1 and ERK phosphorylation in the nucleus accumbens core during withdrawal from cocaine self‐administration
Author(s) -
Edwards Scott,
Bachtell Ryan K.,
Guzman Daniel,
Whisler Kimberly N.,
Self David W.
Publication year - 2011
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/j.1369-1600.2010.00296.x
Subject(s) - nucleus accumbens , context (archaeology) , self administration , phosphorylation , mapk/erk pathway , psychology , addiction , pharmacology , medicine , endocrinology , neuroscience , chemistry , dopamine , biology , biochemistry , paleontology
Reexposure to cocaine‐associated environments promotes relapse to cocaine seeking and represents a persistent impediment to successful abstinence. Neurobiological adaptations are thought to underlie the preservation of drug‐seeking behavior during protracted withdrawal periods, possibly including changes associated specifically with cocaine‐paired contexts. We measured GluR 1 S845 and extracellular signal‐regulated kinase (ERK) phosphorylation in rat striatal subregions in an animal model of cocaine relapse. Animals with cocaine self‐administration experience and their yoked partners were exposed to extinction conditions for one hour in the drug‐paired environmental context after one day or three weeks withdrawal to measure protein phosphorylation induced by the cocaine‐paired context in the absence of cocaine reinforcement. GluR 1 S845 (an index of protein kinase A (PKA) activity) and ERK phosphorylation increased in the nucleus accumbens core of self‐administering but not yoked animals after three weeks (but not one day) withdrawal, indicating a time‐dependent emergence of context‐associated protein phosphorylation in this accumbens subregion. In comparison, animals trained to self‐administer sucrose displayed a similar increase in ERK, but not GluR 1 S845 , phosphorylation following reexposure to a sucrose‐paired environment three weeks later, indicating that GluR 1 S845 phosphorylation did not result solely from lever press behavior per se . In contrast, basal (home cage) GluR 1 S845 phosphorylation was elevated in the nucleus accumbens shell and caudate‐putamen after one day or three weeks cocaine withdrawal regardless of context exposure. These results suggest that time‐dependent emergence of context‐associated GluR 1 S845 phosphorylation in the nucleus accumbens core may contribute to the persistence of cocaine‐seeking behavior, whereas ERK phosphorylation may be a consequence of this behavior.