Effects of antipsychotic drugs on BDNF, GSK-3β, and β-catenin expression in rats subjected to immobilization stress

Abstract

Brain-derived neurotrophic factor (BDNF), glycogen synthase kinase-3β (GSK-3β), and β-catenin have been reported to be altered in patients with schizophrenia and have been targeted by antipsychotic drugs. Atypical antipsychotics, but not typical antipsychotics, exert neuroprotective effects by regulating these proteins. In this study, we analyzed the effects of the atypical antipsychotic drugs olanzapine and aripiprazole and a typical antipsychotic drug, haloperidol, on the expression of BDNF, phosphorylated GSK-3β, and β-catenin in the hippocampus of rats subjected to immobilization stress. Rats were subjected to immobilization stress 6h/day for 3 weeks. The effects of olanzapine (2 mg/kg), aripiprazole (1.5 mg/kg), and haloperidol (1.0 mg/kg) were determined on BDNF, serine⁹-phosphorylated GSK-3β, and β-catenin expression by Western blotting. Immobilization stress significantly decreased the expression of BDNF, phosphorylated GSK-3β, and β-catenin in the hippocampus. Chronic administration of olanzapine and aripiprazole significantly attenuated the decreased expression of these proteins in the hippocampus of rats caused by immobilization stress, and significantly increased the levels of these proteins even without the immobilization stress. However, chronic haloperidol had no such effect. These results suggest that olanzapine and aripiprazole may exert beneficial effects by upregulating BDNF, phosphorylated GSK-3β, and β-catenin in patients with schizophrenia.