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Hyperactive mice show elevated D2High receptors, a model for schizophrenia: calcium/calmodulin‐dependent kinase II alpha knockouts
Author(s) -
Novak Gabriela,
Seeman Philip
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.907.10
Subject(s) - striatum , endocrinology , dopamine receptor d2 , receptor , medicine , chemistry , calmodulin , dopamine , calcium , biology
The cerebral frontal cortex of schizophrenia patients shows elevated levels of RNA for calcium/calmodulin‐dependent protein kinase II beta (CaMKIIβ). In addition, recent research shows that animal models for schizophrenia consistently show elevated levels of dopamine 2 receptors in their high‐affinity state (D2High), the major target for antipsychotic medication. The present study was done to examine whether an alteration in the levels of CaMKIIβ, in respect to CaMKIIα, could lead to altered levels of D2High receptors. We used quantitative real‐time PCR to measure CaMKIIα and CaMKIIβ mRNA levels in heterozygous and wild type CaMKIIα knock‐out mice, which show reduced CaMKIIα levels, and a D2R binding assay to determine the levels of D2High. The heterozygous CaMKIIα knock‐out mice, which show features analogous to schizophrenia, showed a 50% reduction in CaMKIIα mRNA, and no change in CaMKIIβ in the frontal cortex, as expected, but also a 29% upregulation of CaMKIIβ mRNA in the striatum and a 2.8‐fold increase in D2High receptors. In addition, we found that the CaMKII inhibitor, KN‐93, markedly reduced D2High states in rat striatum. The elevated levels of CaMKIIβ mRNA in the striatum suggest that this enzyme may increase D2High in animals and possibly in schizophrenia itself.