RGD Reference Report - Disrupted circadian expression of β-arrestin 2 affects reward-related µ-opioid receptor function in alcohol dependence. - Rat Genome Database

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Disrupted circadian expression of β-arrestin 2 affects reward-related µ-opioid receptor function in alcohol dependence.

Authors: Meinhardt, Marcus W  Giannone, Francesco  Hirth, Nathalie  Bartsch, Dusan  Spampinato, Santi M  Kelsch, Wolfgang  Spanagel, Rainer  Sommer, Wolfgang H  Hansson, Anita C 
Citation: Meinhardt MW, etal., J Neurochem. 2022 Feb;160(4):454-468. doi: 10.1111/jnc.15559. Epub 2022 Jan 4.
RGD ID: 401938593
Pubmed: PMID:34919270   (View Abstract at PubMed)
DOI: DOI:10.1111/jnc.15559   (Journal Full-text)

There is increasing evidence for a daily rhythm of µ-opioid receptor (MOR) efficacy and the development of alcohol dependence. Previous studies show that β-arrestin 2 (bArr2) has an impact on alcohol intake, at least partially mediated via modulation of MOR signaling, which in turn mediates the alcohol rewarding effects. Considering the interplay of circadian rhythms on MOR and alcohol dependence, we aimed to investigate bArr2 in alcohol dependence at different time points of the day/light cycle on the level of bArr2 mRNA (in situ hybridization), MOR availability (receptor autoradiography), and MOR signaling (Damgo-stimulated G-protein coupling) in the nucleus accumbens of alcohol-dependent and non-dependent Wistar rats. Using a microarray data set we found that bArr2, but not bArr1, shows a diurnal transcription pattern in the accumbens of naïve rats with higher expression levels during the active cycle. In 3-week abstinent rats, bArr2 is up-regulated in the accumbens at the beginning of the active cycle (ZT15), whereas no differences were found at the beginning of the inactive cycle (ZT3) compared with controls. This effect was accompanied by a specific down-regulation of MOR binding in the active cycle. Additionally, we detect a higher receptor coupling during the inactive cycle compared with the active cycle in alcohol-dependent animals. Together, we report daily rhythmicity for bArr2 expression linked to an inverse pattern of MOR, suggesting an involvement for bArr2 on circadian regulation of G-protein coupled receptors in alcohol dependence. The presented data may have implications for the development of novel bArr2-related treatment targets for alcoholism.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ARRB2Humanalcohol dependence  ISOArrb2 (Rattus norvegicus)mRNA:decreased expression:nucleus accumbensRGD 
Arrb2Ratalcohol dependence  IEP mRNA:decreased expression:nucleus accumbensRGD 
Arrb2Mousealcohol dependence  ISOArrb2 (Rattus norvegicus)mRNA:decreased expression:nucleus accumbensRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Arrb2Ratcircadian rhythm  IEP  RGD 
Arrb2Ratnegative regulation of opioid receptor signaling pathway  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Arrb2  (arrestin, beta 2)

Genes (Mus musculus)
Arrb2  (arrestin, beta 2)

Genes (Homo sapiens)
ARRB2  (arrestin beta 2)


Additional Information