The orphan GPCR, GPR88, modulates function of the striatal dopamine system: a possible therapeutic target for psychiatric disorders?
Mol Cell Neurosci
; 42(4): 438-47, 2009 Dec.
Article
em En
| MEDLINE
| ID: mdl-19796684
ABSTRACT
In rodents, the orphan G protein-coupled receptor, Gpr88, is highly expressed in brain regions implicated in the pathophysiology of and is modulated by treatments for schizophrenia. We compared striatal function of Gpr88 knockout mice (Gpr88KOs) to wild-type mice using molecular, neurochemical and behavioral tests. Gpr88KOs lacked expression of Gpr88 in striatum, nucleus accumbens and layer IV of cortex. Gpr88KOs had normal striatal dopamine D2 receptor density and affinity and DARPP-32 expression but Gpr88KOs had higher basal striatal phosphorylated DARPP-32 Thr-34. In vivo microdialysis detected lower basal dopamine in Gpr88KOs while amphetamine-induced dopamine release was normal. Behaviorally, Gpr88KOs demonstrated disrupted prepulse inhibition of startle (PPI) and increased sensitivity to apomorphine-induced climbing and stereotypy (AICS) and amphetamine-stimulated locomotor activity. Antipsychotic administration to Gpr88KOs normalized the PPI deficit and blocked AICS. The modulatory role of Gpr88 in striatal dopamine function suggests it may be a new target for treatments for psychiatric disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dopamina
/
Corpo Estriado
/
Receptores Acoplados a Proteínas G
Limite:
Animals
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Female
/
Humans
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Male
Idioma:
En
Revista:
Mol Cell Neurosci
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos