Proteomics

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Cocaine and Environmental Enrichment Proteomics Study of Rat Nucleus Accumbens


ABSTRACT: Prior research demonstrated that environmental enrichment creates individual differences in behavior leading to a protective addiction phenotype in rats. Understanding the mechanisms underlying this phenotype will guide selection of targets for much-needed novel pharmacotherapeutics. The current study investigates basal differences in proteome expression in the nucleus accumbens of enriched and isolated rats and the proteomic response to cocaine self-administration using a liquid chromatography mass spectrometry (LCMS) technique to quantify 1917 proteins. Results of complementary Ingenuity Pathways Analyses (IPA) and gene set enrichment analyses (GSEA) demonstrate that cocaine increases vesicular transporters for dopamine and glutamate, as well as increasing proteins in the RhoA pathway. Further, cocaine regulates proteins related to ERK, CREB and AKT signaling. Environmental enrichment altered expression of a large number of proteins with diverse functions, including mood disorders, energy production, ubiquitination, splicing, transport, kinases and neurodegenerative diseases. Most of the biological functions and pathways listed above were also identified in the Cocaine X Enrichment interaction analysis, providing clear evidence that enriched and isolated rats respond quite differently to cocaine exposure. The overall impression of the current results is that enriched saline-administering rats have a unique proteomic complement compared to enriched cocaine-administering rats as well as saline and cocaine-taking isolated rats. These results identify possible mechanisms of the protective phenotype and provide fertile soil for developing novel pharmacotherapeutics.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Cheryl Lichti  

LAB HEAD: Thomas Green

PROVIDER: PXD000990 | Pride | 2014-07-22

REPOSITORIES: Pride

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Publications

Environmental enrichment alters protein expression as well as the proteomic response to cocaine in rat nucleus accumbens.

Lichti Cheryl F CF   Fan Xiuzhen X   English Robert D RD   Zhang Yafang Y   Li Dingge D   Kong Fanping F   Sinha Mala M   Andersen Clark R CR   Spratt Heidi H   Luxon Bruce A BA   Green Thomas A TA  

Frontiers in behavioral neuroscience 20140721


Prior research demonstrated that environmental enrichment creates individual differences in behavior leading to a protective addiction phenotype in rats. Understanding the mechanisms underlying this phenotype will guide selection of targets for much-needed novel pharmacotherapeutics. The current study investigates differences in proteome expression in the nucleus accumbens of enriched and isolated rats and the proteomic response to cocaine self-administration using a liquid chromatography mass s  ...[more]

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