Valproate prevents MK801-induced changes in brain-derived neurotrophic factor mRNA in the rat brain

To investigate whether the anticonvulsant valproate influences the changes in brain-derived neurotrophic factor (BDNF) mRNA expression induced by MK801 in rat brain, we injected valproate prior to MK801 and observed the changes in the BDNF expression 3 h later. MK801 significantly increased BDNF expression in the retrosplenial and entorhinal cortex, and these increases were prevented by valproate pretreatment. Valproate pretreatment significantly blocked the MK801-induced increase of BDNF expression in retrosplenial cortex at 3 h, 6 h, and 9 h after MK801 injection, suggesting that valproate pretreatment did not delay the MK801-induced increase of BDNF expression. However, MK801 significantly decreased BDNF expression in the granule cell layer of hippocampus, and valproate pretreatment before MK801 potentiated the MK801-induced decrease in BDNF expression in granule cell layer. These results indicate that valproate pretreatment differentially affects the MK801-induced changes in BDNF expression in a region-selective manner.