Expression of brain-derived neurotrophic factor mRNA in rat hippocampus after treatment with antipsychotic drugs.
Typical and atypical antipsychotic drugs, though both effective, act on different neurotransmitter receptors and are dissimilar in some clinical effects and side effects. The typical antipsychotic drug haloperidol has been shown to cause a decrease in the expression of brain-derived neurotrophic factor (BDNF), which plays an important role in neuronal cell survival, differentiation, and neuronal connectivity. However, it is still unknown whether atypical antipsychotic drugs similarly regulate BDNF expression. We examined the effects of chronic (28 days) administration of typical and atypical antipsychotic drugs on BDNF mRNA expression in the rat hippocampus using in situ hybridization. Quantitative analysis revealed that the typical antipsychotic drug haloperidol (1 mg/kg) down-regulated BDNF mRNA expression in both CA1 (P < 0.05) and dentate gyrus (P < 0.01) regions compared with vehicle control. In contrast, the atypical antipsychotic agents clozapine (10 mg/kg) and olanzapine (2.7 mg/kg) up-regulated BDNF mRNA expression in CA1, CA3, and dentate gyrus regions of the rat hippocampus compared with their respective controls (P < 0.01). These findings demonstrate that the typical and atypical antipsychotic drugs differentially regulate BDNF mRNA expression in rat hippocampus.
Bai
Ou
O
Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Chlan-Fourney
Jennifer
J
Bowen
Rudy
R
Keegan
David
D
Li
Xin-Min
XM
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D003024:Clozapine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D017403:In Situ Hybridization / Q000379:methods; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D015259:Dopamine Agents; D012333:RNA, Messenger; D001569:Benzodiazepines; D010890:Pirenzepine; D007980:Levodopa; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine