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

Cheryl F. Lichti, Xiuzhen Fan, Robert D. English, Yafang Zhang, Dingge Li, Fanping Kong, Mala Sinha, Clark R. Andersen, Heidi Spratt, Bruce A. Luxon, Thomas Green

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 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), both performed using protein quantitative data, 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 implicated in a diverse number of neuronal functions (e.g., energy production, mRNA splicing, and ubiquitination), molecular cascades (e.g., protein kinases), psychiatric disorders (e.g., mood disorders), and neurodegenerative diseases (e.g., Huntington's and Alzheimer's diseases). Upregulation of energy metabolism components in EC rats was verified using RNA sequencing. 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. Proteomics data are available via ProteomeXchange with identifier PXD000990.

Original languageEnglish (US)
Article number246
JournalFrontiers in Behavioral Neuroscience
Volume8
Issue numberJULY
DOIs
StatePublished - Jul 21 2014

Fingerprint

Nucleus Accumbens
Cocaine
Proteomics
Proteins
Phenotype
Vesicular Glutamate Transport Proteins
rhoA GTP-Binding Protein
RNA Sequence Analysis
Self Administration
Ubiquitination
Huntington Disease
Proteome
Mood Disorders
Individuality
Liquid Chromatography
Neurodegenerative Diseases
Protein Kinases
Energy Metabolism
Psychiatry
Mass Spectrometry

Keywords

  • Cocaine
  • Differential rearing
  • Drug abuse
  • Drug addiction
  • Label-free quantification
  • Proteomics

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Neuropsychology and Physiological Psychology

Cite this

Environmental enrichment alters protein expression as well as the proteomic response to cocaine in rat nucleus accumbens. / Lichti, Cheryl F.; Fan, Xiuzhen; English, Robert D.; Zhang, Yafang; Li, Dingge; Kong, Fanping; Sinha, Mala; Andersen, Clark R.; Spratt, Heidi; Luxon, Bruce A.; Green, Thomas.

In: Frontiers in Behavioral Neuroscience, Vol. 8, No. JULY, 246, 21.07.2014.

Research output: Contribution to journalArticle

Lichti, Cheryl F. ; Fan, Xiuzhen ; English, Robert D. ; Zhang, Yafang ; Li, Dingge ; Kong, Fanping ; Sinha, Mala ; Andersen, Clark R. ; Spratt, Heidi ; Luxon, Bruce A. ; Green, Thomas. / Environmental enrichment alters protein expression as well as the proteomic response to cocaine in rat nucleus accumbens. In: Frontiers in Behavioral Neuroscience. 2014 ; Vol. 8, No. JULY.
@article{58d4c348295742ad81a4cfb7a9513c66,
title = "Environmental enrichment alters protein expression as well as the proteomic response to cocaine in 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 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), both performed using protein quantitative data, 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 implicated in a diverse number of neuronal functions (e.g., energy production, mRNA splicing, and ubiquitination), molecular cascades (e.g., protein kinases), psychiatric disorders (e.g., mood disorders), and neurodegenerative diseases (e.g., Huntington's and Alzheimer's diseases). Upregulation of energy metabolism components in EC rats was verified using RNA sequencing. 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. Proteomics data are available via ProteomeXchange with identifier PXD000990.",
keywords = "Cocaine, Differential rearing, Drug abuse, Drug addiction, Label-free quantification, Proteomics",
author = "Lichti, {Cheryl F.} and Xiuzhen Fan and English, {Robert D.} and Yafang Zhang and Dingge Li and Fanping Kong and Mala Sinha and Andersen, {Clark R.} and Heidi Spratt and Luxon, {Bruce A.} and Thomas Green",
year = "2014",
month = "7",
day = "21",
doi = "10.3389/fnbeh.2014.00246",
language = "English (US)",
volume = "8",
journal = "Frontiers in Behavioral Neuroscience",
issn = "1662-5153",
publisher = "Frontiers Research Foundation",
number = "JULY",

}

TY - JOUR

T1 - Environmental enrichment alters protein expression as well as the proteomic response to cocaine in rat nucleus accumbens

AU - Lichti, Cheryl F.

AU - Fan, Xiuzhen

AU - English, Robert D.

AU - Zhang, Yafang

AU - Li, Dingge

AU - Kong, Fanping

AU - Sinha, Mala

AU - Andersen, Clark R.

AU - Spratt, Heidi

AU - Luxon, Bruce A.

AU - Green, Thomas

PY - 2014/7/21

Y1 - 2014/7/21

N2 - 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 spectrometry (LCMS) technique to quantify 1917 proteins. Results of complementary Ingenuity Pathways Analyses (IPA) and gene set enrichment analyses (GSEA), both performed using protein quantitative data, 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 implicated in a diverse number of neuronal functions (e.g., energy production, mRNA splicing, and ubiquitination), molecular cascades (e.g., protein kinases), psychiatric disorders (e.g., mood disorders), and neurodegenerative diseases (e.g., Huntington's and Alzheimer's diseases). Upregulation of energy metabolism components in EC rats was verified using RNA sequencing. 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. Proteomics data are available via ProteomeXchange with identifier PXD000990.

AB - 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 spectrometry (LCMS) technique to quantify 1917 proteins. Results of complementary Ingenuity Pathways Analyses (IPA) and gene set enrichment analyses (GSEA), both performed using protein quantitative data, 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 implicated in a diverse number of neuronal functions (e.g., energy production, mRNA splicing, and ubiquitination), molecular cascades (e.g., protein kinases), psychiatric disorders (e.g., mood disorders), and neurodegenerative diseases (e.g., Huntington's and Alzheimer's diseases). Upregulation of energy metabolism components in EC rats was verified using RNA sequencing. 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. Proteomics data are available via ProteomeXchange with identifier PXD000990.

KW - Cocaine

KW - Differential rearing

KW - Drug abuse

KW - Drug addiction

KW - Label-free quantification

KW - Proteomics

UR - http://www.scopus.com/inward/record.url?scp=84904612542&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904612542&partnerID=8YFLogxK

U2 - 10.3389/fnbeh.2014.00246

DO - 10.3389/fnbeh.2014.00246

M3 - Article

AN - SCOPUS:84904612542

VL - 8

JO - Frontiers in Behavioral Neuroscience

JF - Frontiers in Behavioral Neuroscience

SN - 1662-5153

IS - JULY

M1 - 246

ER -