Title | Enhanced CREB and DARPP-32 phosphorylation in the nucleus accumbens and CREB, ERK, and GluR1 phosphorylation in the dorsal hippocampus is associated with cocaine-conditioned place preference behavior. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Tropea TF, Kosofsky BE, Rajadhyaksha AM |
Journal | J Neurochem |
Volume | 106 |
Issue | 4 |
Pagination | 1780-90 |
Date Published | 2008 Aug |
ISSN | 1471-4159 |
Keywords | Animals, Cocaine, Conditioning (Psychology), Cyclic AMP Response Element-Binding Protein, Dopamine and cAMP-Regulated Phosphoprotein 32, Extracellular Signal-Regulated MAP Kinases, Hippocampus, Mice, Mice, Inbred C57BL, Nucleus Accumbens, Phosphorylation, Receptors, AMPA, Telencephalon |
Abstract | Environment-induced relapse is a major concern in drug addiction because of the strong associations formed between drug reward and environment. Cocaine-conditioned place preference is an ideal experimental tool to examine adaptations in the molecular pathways that are activated upon re-exposure to an environment previously paired with drug reward. To better understand the mechanism of cocaine-conditioned place preference we have used western blot analysis to examine changes in phosphorylation of cAMP-response element binding protein (CREB), dopamine- and cyclic AMP-regulated phosphoprotein 32 (DARPP-32), extracellular signal-regulated kinase (ERK) and GluR1, key molecular substrates altered by cocaine, in the nucleus accumbens (NAc) and dorsal hippocampus (DHC) of C57BL/6 mice. Our studies revealed that re-exposing mice to an environment in which they were previously given cocaine resulted in increased levels of Ser133 phospho-CREB and Thr34 phospho-DARPP-32 with a corresponding decrease in Thr75 phospho-DARPP-32 in the NAc. In DHC there were increased levels of phospho-CREB, Thr183/Tyr185 phospho-ERK, and Ser845 phospho-GluR1. These data suggest that the formation of contextual drug reward associations involves recruitment of the DHC-NAc circuit with activation of the DARPP-32/CREB pathway in the NAc and the ERK/CREB pathway in the DHC. |
DOI | 10.1111/j.1471-4159.2008.05518.x |
Alternate Journal | J. Neurochem. |
PubMed ID | 18554320 |
PubMed Central ID | PMC2706979 |
Grant List | K01 DA014057 / DA / NIDA NIH HHS / United States K01 DA014057-05 / DA / NIDA NIH HHS / United States K02 DA000354 / DA / NIDA NIH HHS / United States KO2DA00354 / DA / NIDA NIH HHS / United States |