RGD Reference Report - Persistent pain maintains morphine-seeking behavior after morphine withdrawal through reduced MeCP2 repression of GluA1 in rat central amygdala. - Rat Genome Database

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Persistent pain maintains morphine-seeking behavior after morphine withdrawal through reduced MeCP2 repression of GluA1 in rat central amygdala.

Authors: Hou, Yuan-Yuan  Cai, You-Qing  Pan, Zhizhong Z 
Citation: Hou YY, etal., J Neurosci. 2015 Feb 25;35(8):3689-700. doi: 10.1523/JNEUROSCI.3453-14.2015.
RGD ID: 401976466
Pubmed: PMID:25716866   (View Abstract at PubMed)
PMCID: PMC4339367   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.3453-14.2015   (Journal Full-text)

As long-term opioids are increasingly used for control of chronic pain, how pain affects the rewarding effect of opioids and hence risk of prescription opioid misuse and abuse remains a healthcare concern and a challenging issue in current pain management. In this study, using a rat model of morphine self-administration, we investigated the molecular mechanisms underlying the impact of pain on operant behavior of morphine intake and morphine seeking before and after morphine withdrawal. We found that rats with persistent pain consumed a similar amount of daily morphine to that in control rats without pain, but maintained their level-pressing behavior of morphine seeking after abstinence of morphine at 0.2 mg/kg, whereas this behavior was gradually diminished in control rats. In the central nucleus of amygdala (CeA), a limbic structure critically involved in the affective dimension of pain, proteins of GluA1 subunits of glutamate AMPA receptors were upregulated during morphine withdrawal, and viral knockdown of CeA GluA1 eliminated the morphine-seeking behavior in withdrawn rats of the pain group. Chromatin immunoprecipitation analysis revealed that the methyl CpG-binding protein 2 (MeCP2) was enriched in the promoter region of Gria1 encoding GluA1 and this enrichment was significantly attenuated in withdrawn rats of the pain group. Furthermore, viral overexpression of CeA MeCP2 repressed the GluA1 level and eliminated the maintenance of morphine-seeking behavior after morphine withdrawal. These results suggest direct MeCp2 repression of GluA1 function as a likely mechanism for morphine-seeking behavior maintained by long-lasting affective pain after morphine withdrawal.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GRIA1Humanmorphine dependence  ISOGria1 (Rattus norvegicus) RGD 
Gria1Ratmorphine dependence  IMP  RGD 
Gria1Mousemorphine dependence  ISOGria1 (Rattus norvegicus) RGD 
GRIA1Humanmorphine withdrawal syndrome  ISOGria1 (Rattus norvegicus)associated with Pain and protein:increased expression:central amygdaloid nucleus (rat)RGD 
Gria1Ratmorphine withdrawal syndrome  IEP associated with Pain and protein:increased expression:central amygdaloid nucleus (rat)RGD 
Gria1Ratmorphine withdrawal syndrome  IMP  RGD 
Gria1Mousemorphine withdrawal syndrome  ISOGria1 (Rattus norvegicus)associated with Pain and protein:increased expression:central amygdaloid nucleus (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gria1Ratbehavioral response to pain  IEP  RGD 
Gria1Ratresponse to morphine  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gria1  (glutamate ionotropic receptor AMPA type subunit 1)

Genes (Mus musculus)
Gria1  (glutamate receptor, ionotropic, AMPA1 (alpha 1))

Genes (Homo sapiens)
GRIA1  (glutamate ionotropic receptor AMPA type subunit 1)


Additional Information