AI Article Synopsis
- The study investigates the role of the Gpr88 receptor in brain function related to schizophrenia using genetically modified mice.
- Gpr88 knockout mice displayed altered dopamine levels and abnormal behavioral responses compared to normal mice, indicating the receptor's influence on striatal function.
- Treatment with antipsychotics restored certain behavioral deficits in Gpr88 knockout mice, suggesting Gpr88 as a potential target for new psychiatric disorder therapies.
Article 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.
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| http://dx.doi.org/10.1016/j.mcn.2009.09.007 | DOI Listing |
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