RGD Reference Report - G protein-coupled receptor kinase 6/beta-arrestin 2 system in a rat model of dopamine supersensitivity psychosis. - Rat Genome Database

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G protein-coupled receptor kinase 6/beta-arrestin 2 system in a rat model of dopamine supersensitivity psychosis.

Authors: Oda, Y  Tadokoro, S  Takase, M  Kanahara, N  Watanabe, H  Shirayama, Y  Hashimoto, K  Iyo, M 
Citation: Oda Y, etal., J Psychopharmacol. 2015 Dec;29(12):1308-13. doi: 10.1177/0269881115593903. Epub 2015 Jul 14.
RGD ID: 11534754
Pubmed: PMID:26174132   (View Abstract at PubMed)
DOI: DOI:10.1177/0269881115593903   (Journal Full-text)

In humans, long-term antipsychotic treatment is known to induce movement disorders and a psychosis, called dopamine supersensitivity psychosis (DSP). The mechanism by which chronic administration of antipsychotic(s) causes DSP may be the treatment-induced up-regulation of dopamine D2 receptors (DRD2). G protein-coupled receptor kinase 6 (GRK6) and beta-arrestin 2 (ARRB2) play important roles in the trafficking of DRD2 by phosphorylation and internalization. We investigated the effects of chronic continuous treatment with mini-pump-administered haloperidol (HAL) on the sensitivity of Wistar rats to dopamine, as measured by the locomotor response to methamphetamine (MAP) and the density of striatal DRD2. Chronic continuous treatment with HAL resulted in significantly higher locomotor response to MAP and significantly higher striatal DRD2 density compared with those in rats administered vehicle (VEH). Enzyme-linked immunosorbent assays revealed that striatal ARRB2 in DSP model rats tended to decrease in comparison with that in the VEH group. In addition, the ratio of GRK6/ARRB2 in DSP model rats was significantly higher than that in controls. Our results suggest that alterations of the GRK6 and ARRB2 system could induce both DRD2 up-regulation and impairment of the dopamine signaling pathway, resulting potentially in the development of DSP.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
drug psychosis  ISOArrb2 (Rattus norvegicus)11534754; 11534754protein:increased expression:striatumRGD 
drug psychosis  IEP 11534754protein:increased expression:striatumRGD 
drug psychosis  ISODrd2 (Rattus norvegicus)11534754; 11534754 RGD 
drug psychosis  IEP 11534754 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Arrb2  (arrestin, beta 2)
Drd2  (dopamine receptor D2)

Genes (Mus musculus)
Arrb2  (arrestin, beta 2)
Drd2  (dopamine receptor D2)

Genes (Homo sapiens)
ARRB2  (arrestin beta 2)
DRD2  (dopamine receptor D2)


Additional Information