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Hyperactive mice show elevated D2 High receptors, a model for schizophrenia: Calcium/calmodulin‐dependent kinase II alpha knockouts
Author(s) -
Novak Gabriela,
Seeman Philip
Publication year - 2010
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20786
Subject(s) - striatum , dopamine receptor d2 , endocrinology , medicine , receptor , calmodulin , chemistry , schizophrenia (object oriented programming) , dopamine , calcium , biology , psychiatry
Abstract The cerebral frontal cortex of patients who had schizophrenia shows elevated levels of RNA for calcium/calmodulin‐dependent protein kinase II beta (CaMKIIβ). In addition, recent research shows that animal models for schizophrenia, such as amphetamine‐sensitized rats, consistently show elevated levels of D2 receptors in their high‐affinity state (D2 High ), the major target for antipsychotic medication. The present study was done, therefore, to examine whether an alteration in the levels of CaMKIIβ could lead to altered levels of D2 High receptors. We found that the CaMKII inhibitor, KN‐93, markedly reduced D2 High states in rat striatum. In addition, we studied heterozygous CaMKIIα knock‐out mice that show features analogous to schizophrenia. The striata of these mice revealed a 2.8‐fold increase in D2 High receptors. In frontal cortex of the heterozygous CaMKIIα knock‐out mice, CaMKIIα mRNA levels were reduced by 50%, while CaMKIIβ mRNA levels were unaltered. In striatum, CaMKIIβ mRNA levels were increased by 29%, suggesting the presence of a new CaMKIIβ regulatory pathway not previously described. The elevated levels of CaMKIIβ mRNA in the striatum suggest that this enzyme may increase D2 High in animals and possibly in schizophrenia itself. Synapse 64:794–800, 2010. © 2010 Wiley‐Liss, Inc.