Antipsychotic drug treatment induces differential gene expression in the rat cortex.
Antipsychotic drug treatment is known to modulate gene expression in experimental animals. In this study, candidate target genes for antipsychotic drug action were searched using microarrays after acute clozapine treatment (1, 6 and 24 h) in the rat prefrontal cortex. Microarray data clustering with a self-organizing map algorithm revealed differential expression of genes involved in presynaptic function following acute clozapine treatment. The differential expression of 35 genes most profoundly regulated in expression arrays was further examined using in situ hybridization following acute clozapine, and chronic clozapine and haloperidol treatments. Acute administration of clozapine regulated the expression of chromogranin A, synaptotagmin V and calcineurin A mRNAs in the cortex. Chronic clozapine treatment induced differential cortical expression of chromogranin A, son of sevenless (SoS) and Sec-1. Chronic treatment with haloperidol regulated the mRNA expression of inhibitor of DNA-binding 2 (ID-2) and Rab-12. Furthermore, the expression of visinin-like proteins-1, -2 and -3 was regulated by chronic drug treatments in various brain regions. Our data suggest that acute and chronic treatments with haloperidol and clozapine modulate the expression of genes involved in synaptic function and in regulation of intracellular Ca2+ in cortex.
Kontkanen
Outi
O
A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland Department of Psychiatry, University of Kuopio, Kuopio, Finland.
Törönen
Petri
P
Lakso
Merja
M
Wong
Garry
G
Castrén
Eero
E
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D053379:Chromogranin A; D002864:Chromogranins / Q000235:genetics / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D017403:In Situ Hybridization; D051797:Inhibitor of Differentiation Protein 2; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins; D020664:Son of Sevenless Proteins / Q000235:genetics / Q000378:metabolism; D050857:Synaptotagmins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D014150:Antipsychotic Agents; D002135:Calcium-Binding Proteins; D053379:Chromogranin A; D002864:Chromogranins; D004268:DNA-Binding Proteins; C497451:Id2 protein, rat; D051797:Inhibitor of Differentiation Protein 2; D008562:Membrane Glycoproteins; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D020664:Son of Sevenless Proteins; C494297:Syt5 protein, rat; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; D050857:Synaptotagmins; D019703:Calcineurin; D020691:rab GTP-Binding Proteins; D003024:Clozapine; D006220:Haloperidol