title: Impact of haloperidol and risperidone on gene expression profile in the rat cortex.
abstract: Despite the clinical efficacy of the most thoroughly studied conventional neuroleptic agent haloperidol, and the atypical antipsychotic risperidone is well established, little information is available on their molecular effects. Recent advances in high-density DNA microarray techniques allow the possibility to analyze thousands of genes simultaneously for their differential gene expression patterns in various biological processes, and to determine mechanisms of drug action. The aim of this series of experiments was to gain experience in antipsychotic gene-expression profiling and characterize (in the parlance of genomics) the "antipsychotic transcriptome." In this prospective animal study, broad-scale gene expression profiles were characterized for brains of rats treated with antipsychotics and compared with those of sham controls. We used DNA microarrays containing 8000 sequences to measure the expression patterns of multiple genes in rat fronto-temporo-parietal cortex after intraperitoneal treatment with haloperidol or risperidone. A number of transcripts were differentially expressed between control and treated samples, of which only 36 and 89 were found to significantly differ in expression as a result of exposure to haloperidol or risperidone, respectively (P<0.05). Acutely, 13 genes were more highly expressed and 15 transcripts were found to be significantly less abundant, whereas chronically nine genes were up-regulated and none of them was repressed in haloperidol-treated cortices. Risperidone acutely induced 43 and repressed 46 genes, and chronically over-expressed 6 and down-regulated 11 transcripts. Selected genes were assayed by real-time PCR, then normalized to beta-actin. These assays confirmed the significance of the array results for all transcripts tested. Despite their differing receptor affinity and selectivity, our findings indicate that haloperidol and risperidone interfere with cell survival, neural plasticity, signal transduction, ionic homeostasis and metabolism in a similar manner.
authors.affiliation: Laboratory of Functional Genomics, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Temesvári krt 62, Hungary.
authors.forename: Liliána Z
authors.initials: LZ
authors.lastname: Fehér
authors.forename: János
authors.initials: J
authors.lastname: Kálmán
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
authors.forename: Gábor
authors.initials: G
authors.lastname: Gyülvészi
authors.forename: Klára
authors.initials: K
authors.lastname: Kitajka
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: Miklós
authors.initials: M
authors.lastname: Palotás
authors.forename: Elena I
authors.initials: EI
authors.lastname: Samarova
authors.forename: József
authors.initials: J
authors.lastname: Molnár
authors.forename: Agnes
authors.initials: A
authors.lastname: Zvara
authors.forename: Keyvan
authors.initials: K
authors.lastname: Matin
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Bódi
authors.forename: Marietta
authors.initials: M
authors.lastname: Hugyecz
authors.forename: Magdolna
authors.initials: M
authors.lastname: Pákáski
authors.forename: Annamária
authors.initials: A
authors.lastname: Bjelik
authors.forename: Anna
authors.initials: A
authors.lastname: Juhász
authors.forename: Gábor
authors.initials: G
authors.lastname: Bogáts
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Janka
authors.forename: András
authors.initials: A
authors.lastname: Palotás
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004334:Drug Administration Schedule; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000494:pharmacology*; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D006220:Haloperidol; D018967:Risperidone