Effect of Haloperidol and Olanzapine on Hippocampal Cells' Proliferation in Animal Model of Schizophrenia.

Abstract

Aberrant neurogenesis in the subventricular zone (SVZ) and hippocampus (HIP) contributes to schizophrenia pathogenesis. Haloperidol (HAL) and olanzapine (OLA), commonly prescribed antipsychotics for schizophrenia treatment, affect neurogenesis too. The effect of HAL and OLA on an mHippoE-2 cell line was studied in vitro where we measured the cell number and projection length. In vivo, we studied the gene expression of,,, andin the SVZ and HIP in an MK-801-induced animal schizophrenia model. Cells were incubated with HAL, OLA, and MK-801 for 24, 48, and 72 h. Animals were injected for 6 days with saline or MK801 (0.5 mg/kg), and from the 7th day with either vehicle HAL (1 mg/kg) or OLA (2 mg/kg), for the next 7 days. In vitro, HAL and OLA dose/time-dependently suppressed cells' proliferation and shortened their projection length. HAL/OLA co-treatment with MK-801 for 24 h reversed HAL's/OLA's inhibitory effect. In vivo, HAL and OLA suppressedandgenes' expression in the HIP and SVZ. MK-801 decreasedandgenes' expression in the HIP and OLA prevented this effect. The data suggest that subchronic HAL/OLA treatment can inhibitandexpression. In an MK-801 schizophrenia model, OLA reversed the MK-801 inhibitory effect onandand HAL reversed the effect on DCX expression; however, only in the HIP.