Effect of antipsychotic drugs on DISC1 and dysbindin expression in mouse frontal cortex and hippocampus.
Altered expression of Disrupted-In-Schizophrenia-1 (DISC1) and dysbindin (DTNBP1), susceptibility genes for schizophrenia, in schizophrenic brain has been reported; however, the possible effect of antipsychotics on the expression levels of these genes has not yet been studied. We measured the mRNA expression levels of these genes in frontal cortex and hippocampus of mice chronically treated with typical and atypical antipsychotics by a real-time quantitative RT-PCR method. We found that atypical antipsychotics, olanzapine and risperidone, in a clinically relevant dose increased DISC1 expression levels in frontal cortex, while a typical antipsychotic, haloperidol, did not. No significant effect on dysbindin expression levels was observed in either brain region. These data suggest that prior evidence of decreased expression of dysbindin in postmortem brain of schizophrenics is not likely to be a simple artifact of antemortem drug treatment. Our results also suggest a potential role of DISC1 in the therapeutic mechanisms of certain atypical antipsychotics.
Chiba
S
S
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan.
Hashimoto
R
R
Hattori
S
S
Yohda
M
M
Lipska
B
B
Weinberger
D R
DR
Kunugi
H
H
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003851:Deoxyribonucleases / Q000737:chemistry; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; D014150:Antipsychotic Agents; C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012313:RNA; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D012194:RNA-Directed DNA Polymerase; D003851:Deoxyribonucleases