Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain

A. A. Pavlovsky, D. Boehning, D. Li, Y. Zhang, X. Fan, Thomas Green

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors activating transcription factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated is unknown. The current study examines transcriptional responses of key ER stress target genes subsequent to psychological stress or cocaine. Rats were subjected to acute or repeated restraint stress or cocaine treatment and mRNA was isolated from dorsal striatum, medial prefrontal cortex and nucleus accumbens brain tissue. ER stress gene mRNA expression was measured using quantitative polymerase chain reaction (PCR) and RNA sequencing. Restraint stress and cocaine-induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components x-box binding protein 1 (XBP1) and ATF6. In addition, rats living in an enriched environment (large group cage with novel toys changed daily) exhibited rapid induction of GADD34 and ATF3 after 30. min of exploring novel toys, suggesting these genes are also involved in normal non-pathological signaling. However, environmental enrichment, a paradigm that produces protective addiction and depression phenotypes in rats, attenuated the rapid induction of ATF3 and GADD34 after restraint stress. These experiments provide a sensitive measure of ER stress and, more importantly, these results offer good evidence of the activation of ER stress mechanisms from psychological stress, cocaine and natural reward. Thus, ER stress genes may be targets for novel therapeutic targets for depression and addiction.

Original languageEnglish (US)
Pages (from-to)160-169
Number of pages10
JournalNeuroscience
Volume246
DOIs
StatePublished - Aug 9 2013

Fingerprint

Endoplasmic Reticulum Stress
Reward
Cocaine
Psychological Stress
Activating Transcription Factor 3
Brain
Genes
Play and Playthings
Depression
RNA Sequence Analysis
Messenger RNA
Nucleus Accumbens
Amphetamine
Prefrontal Cortex
Carrier Proteins
Transcription Factors
Phenotype
Gene Expression
Polymerase Chain Reaction

Keywords

  • $Depression$Addiction$Cellular stress$Environmental enrichment$Differential rearing
  • Addiction
  • Cellular stress
  • Depression
  • Differential rearing
  • Environmental enrichment

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain. / Pavlovsky, A. A.; Boehning, D.; Li, D.; Zhang, Y.; Fan, X.; Green, Thomas.

In: Neuroscience, Vol. 246, 09.08.2013, p. 160-169.

Research output: Contribution to journalArticle

Pavlovsky, A. A. ; Boehning, D. ; Li, D. ; Zhang, Y. ; Fan, X. ; Green, Thomas. / Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain. In: Neuroscience. 2013 ; Vol. 246. pp. 160-169.
@article{5ba55e84396443c2a5d622af1b0ce847,
title = "Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain",
abstract = "Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors activating transcription factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated is unknown. The current study examines transcriptional responses of key ER stress target genes subsequent to psychological stress or cocaine. Rats were subjected to acute or repeated restraint stress or cocaine treatment and mRNA was isolated from dorsal striatum, medial prefrontal cortex and nucleus accumbens brain tissue. ER stress gene mRNA expression was measured using quantitative polymerase chain reaction (PCR) and RNA sequencing. Restraint stress and cocaine-induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components x-box binding protein 1 (XBP1) and ATF6. In addition, rats living in an enriched environment (large group cage with novel toys changed daily) exhibited rapid induction of GADD34 and ATF3 after 30. min of exploring novel toys, suggesting these genes are also involved in normal non-pathological signaling. However, environmental enrichment, a paradigm that produces protective addiction and depression phenotypes in rats, attenuated the rapid induction of ATF3 and GADD34 after restraint stress. These experiments provide a sensitive measure of ER stress and, more importantly, these results offer good evidence of the activation of ER stress mechanisms from psychological stress, cocaine and natural reward. Thus, ER stress genes may be targets for novel therapeutic targets for depression and addiction.",
keywords = "$Depression$Addiction$Cellular stress$Environmental enrichment$Differential rearing, Addiction, Cellular stress, Depression, Differential rearing, Environmental enrichment",
author = "Pavlovsky, {A. A.} and D. Boehning and D. Li and Y. Zhang and X. Fan and Thomas Green",
year = "2013",
month = "8",
day = "9",
doi = "10.1016/j.neuroscience.2013.04.057",
language = "English (US)",
volume = "246",
pages = "160--169",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain

AU - Pavlovsky, A. A.

AU - Boehning, D.

AU - Li, D.

AU - Zhang, Y.

AU - Fan, X.

AU - Green, Thomas

PY - 2013/8/9

Y1 - 2013/8/9

N2 - Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors activating transcription factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated is unknown. The current study examines transcriptional responses of key ER stress target genes subsequent to psychological stress or cocaine. Rats were subjected to acute or repeated restraint stress or cocaine treatment and mRNA was isolated from dorsal striatum, medial prefrontal cortex and nucleus accumbens brain tissue. ER stress gene mRNA expression was measured using quantitative polymerase chain reaction (PCR) and RNA sequencing. Restraint stress and cocaine-induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components x-box binding protein 1 (XBP1) and ATF6. In addition, rats living in an enriched environment (large group cage with novel toys changed daily) exhibited rapid induction of GADD34 and ATF3 after 30. min of exploring novel toys, suggesting these genes are also involved in normal non-pathological signaling. However, environmental enrichment, a paradigm that produces protective addiction and depression phenotypes in rats, attenuated the rapid induction of ATF3 and GADD34 after restraint stress. These experiments provide a sensitive measure of ER stress and, more importantly, these results offer good evidence of the activation of ER stress mechanisms from psychological stress, cocaine and natural reward. Thus, ER stress genes may be targets for novel therapeutic targets for depression and addiction.

AB - Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors activating transcription factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated is unknown. The current study examines transcriptional responses of key ER stress target genes subsequent to psychological stress or cocaine. Rats were subjected to acute or repeated restraint stress or cocaine treatment and mRNA was isolated from dorsal striatum, medial prefrontal cortex and nucleus accumbens brain tissue. ER stress gene mRNA expression was measured using quantitative polymerase chain reaction (PCR) and RNA sequencing. Restraint stress and cocaine-induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components x-box binding protein 1 (XBP1) and ATF6. In addition, rats living in an enriched environment (large group cage with novel toys changed daily) exhibited rapid induction of GADD34 and ATF3 after 30. min of exploring novel toys, suggesting these genes are also involved in normal non-pathological signaling. However, environmental enrichment, a paradigm that produces protective addiction and depression phenotypes in rats, attenuated the rapid induction of ATF3 and GADD34 after restraint stress. These experiments provide a sensitive measure of ER stress and, more importantly, these results offer good evidence of the activation of ER stress mechanisms from psychological stress, cocaine and natural reward. Thus, ER stress genes may be targets for novel therapeutic targets for depression and addiction.

KW - $Depression$Addiction$Cellular stress$Environmental enrichment$Differential rearing

KW - Addiction

KW - Cellular stress

KW - Depression

KW - Differential rearing

KW - Environmental enrichment

UR - http://www.scopus.com/inward/record.url?scp=84878431327&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878431327&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2013.04.057

DO - 10.1016/j.neuroscience.2013.04.057

M3 - Article

VL - 246

SP - 160

EP - 169

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

ER -