Chronic antipsychotics treatment regulates MAOA, MAOB and COMT gene expression in rat frontal cortex.
Chronic antipsychotic drugs treatment may regulate the expression of a variety of genes in the brain, which may underscore their clinical efficacy and/or side effects. In this study, we measured the mRNA levels of three genes encoding the catabolic enzymes of biogenic amine neurotransmitters, i.e., monoamine oxidase A (MAOA), B (MAOB) and catechol O-methyltransferase (COMT), in rat frontal cortex following 4 weeks' treatment of various antipsychotic drugs using quantitative PCR. Significantly elevated mRNA levels of MAOB and COMT were first observed in frontal cortex of rats treated with risperidone (1mg/kg) when compared to control animals. Further study showed that chronic treatment of olanzapine (2mg/kg), but not haloperidol (1mg/kg) or clozapine (20mg/kg), resulted in significantly increased mRNA levels of MAOA, MAOB and COMT in rat frontal cortex as compared to control animals. These results indicate that chronic treatment of different antipsychotic drugs may differentially regulate the gene expression of three catabolic enzymes of biogenic amine neurotransmitters, and which may partly account for the molecular mechanism of their different clinical efficacy.
Chen
Mao-Liang
ML
Institute of Medical Sciences, Tzu-Chi University, Hualien City 970, Taiwan.
Chen
Chia-Hsiang
CH
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D016373:DNA, Antisense / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005625:Frontal Lobe / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008995:Monoamine Oxidase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000077152:Olanzapine; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000008:administration & dosage / Q000494:pharmacology
D014150:Antipsychotic Agents; D017931:DNA Primers; D016373:DNA, Antisense; D012333:RNA, Messenger; D001569:Benzodiazepines; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine