RGD Reference Report - Extinction of aversive memories associated with morphine withdrawal requires ERK-mediated epigenetic regulation of brain-derived neurotrophic factor transcription in the rat ventromedial prefrontal cortex. - Rat Genome Database

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Extinction of aversive memories associated with morphine withdrawal requires ERK-mediated epigenetic regulation of brain-derived neurotrophic factor transcription in the rat ventromedial prefrontal cortex.

Authors: Wang, Wei-Sheng  Kang, Shuo  Liu, Wen-Tao  Li, Mu  Liu, Yao  Yu, Chuan  Chen, Jie  Chi, Zhi-Qiang  He, Ling  Liu, Jing-Gen 
Citation: Wang WS, etal., J Neurosci. 2012 Oct 3;32(40):13763-75. doi: 10.1523/JNEUROSCI.1991-12.2012.
RGD ID: 401938640
Pubmed: PMID:23035088   (View Abstract at PubMed)
PMCID: PMC6704794   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.1991-12.2012   (Journal Full-text)

Recent evidence suggests that histone deacetylase (HDAC) inhibitors facilitate extinction of rewarding memory of drug taking. However, little is known about the role of chromatin modification in the extinction of aversive memory of drug withdrawal. In this study, we used conditioned place aversion (CPA), a highly sensitive model for measuring aversive memory of drug withdrawal, to investigate the role of epigenetic regulation of brain-derived neurotrophic factor (BDNF) gene expression in extinction of aversive memory. We found that CPA extinction training induced an increase in recruiting cAMP response element-binding protein (CREB) to and acetylation of histone H3 at the promoters of BDNF exon I transcript and increased BDNF mRNA and protein expression in the ventromedial prefrontal cortex (vmPFC) of acute morphine-dependent rats and that such epigenetic regulation of BDNF gene transcription could be facilitated or diminished by intra-vmPFC infusion of HDAC inhibitor trichostatin A or extracellular signal-regulated kinase (ERK) inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene) before extinction training. Correspondingly, disruption of the epigenetic regulation of BDNF gene transcription with U0126 or suppression of BDNF signaling with Trk receptor antagonist K252a or BDNF scavenger tyrosine kinase receptor B (TrkB)-Fc blocked extinction of CPA behavior. We also found that extinction training-induced activation of ERK and CREB and extinction of CPA behavior could be potentiated or suppressed by intra-vmPFC infusion of d-cycloserine, a NMDA receptor partial agonist or aminophosphonopentanoic acid, a NMDA receptor antagonist. We conclude that extinction of aversive memory of morphine withdrawal requires epigenetic regulation of BDNF gene transcription in the vmPFC through activation of the ERK-CREB signaling pathway perhaps in a NMDA receptor-dependent manner.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CREB1Humanwithdrawal disorder  ISOCreb1 (Rattus norvegicus)associated with morphine dependence and protein:increased phosphorylation:prefrontal cortexRGD 
Creb1Ratwithdrawal disorder  IDA associated with morphine dependence and protein:increased phosphorylation:prefrontal cortexRGD 
Creb1Mousewithdrawal disorder  ISOCreb1 (Rattus norvegicus)associated with morphine dependence and protein:increased phosphorylation:prefrontal cortexRGD 
MAPK1Humanwithdrawal disorder  ISOMapk1 (Rattus norvegicus)associated with morphine dependence and protein:increased phosphorylation:prefrontal cortexRGD 
MAPK3Humanwithdrawal disorder  ISOMapk3 (Rattus norvegicus)associated with morphine dependence and protein:increased phosphorylation:prefrontal cortexRGD 
Mapk1Ratwithdrawal disorder  IDA associated with morphine dependence and protein:increased phosphorylation:prefrontal cortexRGD 
Mapk1Mousewithdrawal disorder  ISOMapk1 (Rattus norvegicus)associated with morphine dependence and protein:increased phosphorylation:prefrontal cortexRGD 
Mapk3Ratwithdrawal disorder  IDA associated with morphine dependence and protein:increased phosphorylation:prefrontal cortexRGD 
Mapk3Mousewithdrawal disorder  ISOMapk3 (Rattus norvegicus)associated with morphine dependence and protein:increased phosphorylation:prefrontal cortexRGD 

Objects Annotated

Genes (Rattus norvegicus)
Creb1  (cAMP responsive element binding protein 1)
Mapk1  (mitogen activated protein kinase 1)
Mapk3  (mitogen activated protein kinase 3)

Genes (Mus musculus)
Creb1  (cAMP responsive element binding protein 1)
Mapk1  (mitogen-activated protein kinase 1)
Mapk3  (mitogen-activated protein kinase 3)

Genes (Homo sapiens)
CREB1  (cAMP responsive element binding protein 1)
MAPK1  (mitogen-activated protein kinase 1)
MAPK3  (mitogen-activated protein kinase 3)


Additional Information