RGD Reference Report - Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain. - Rat Genome Database

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

Authors: Pavlovsky, AA  Boehning, D  Li, D  Zhang, Y  Fan, X  Green, TA 
Citation: Pavlovsky AA, etal., Neuroscience. 2013 Aug 29;246:160-9. doi: 10.1016/j.neuroscience.2013.04.057. Epub 2013 May 2.
RGD ID: 9999166
Pubmed: PMID:23644055   (View Abstract at PubMed)
PMCID: PMC3691328   (View Article at PubMed Central)
DOI: DOI:10.1016/j.neuroscience.2013.04.057   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to cocaine  IEP 9999166 RGD 
response to environmental enrichment  IEP 9999166 RGD 
response to immobilization stress  IEP 9999166 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppp1r15a  (protein phosphatase 1, regulatory subunit 15A)

Additional Information