Chronic treatment with aripiprazole induces differential gene expression in the rat frontal cortex.
Chronic treatment of antipsychotic drugs can modulate gene expression in the brain, which may underscore their clinical efficacy. Aripiprazole is the first approved antipsychotic drug of the class of dopamine D2 receptor partial agonist, which has been shown to have similar efficacy and favourable side-effects profile compared to other antipsychotic drugs. This study aimed to identify differential gene expression induced by chronic treatment of aripiprazole. We used microarray-based gene expression profiling technology, real-time quantitative PCR and Western blot analysis to identify differentially expressed genes in the frontal cortex of rats under 4 wk treatment of aripiprazole (10 mg/kg). We were able to detect ten up-regulated genes, including early growth response gene 1, 2, 4 (Egr1, Egr2, Egr4), chromobox homolog 7 (Cbx7), cannabinoid receptor (Cnr1), catechol-O-methyltransferase (Comt), protein phosphatase 2c, magnesium dependent (Ppm2c), tachykinin receptor 3 (Tacr3), Wiscott-Aldrich syndrome-like gene (Wasl) and DNA methyltransferase 3a (Dnmt3a). Our data indicate that chronic administration of aripiprazole can induce differential expression of genes involved in transcriptional regulation and chromatin remodelling and genes implicated in the pathogenesis of psychosis.
Cheng
Min-Chih
MC
Institute of Medical Sciences, Tzu-Chi University, Hualien City, Taiwan.
Liao
Ding-Lieh
DL
Hsiung
Chao A
CA
Chen
Chih-Yu
CY
Liao
Yu-Chieh
YC
Chen
Chia-Hsiang
CH
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D012333:RNA, Messenger; D000068180:Aripiprazole