Olanzapine counteracts reduction of brain-derived neurotrophic factor and TrkB receptors in rat hippocampus produced by haloperidol

Recently, we have reported studies in rats showing that the atypical antipsychotic olanzapine (OLZ), in contrast to haloperidol (HAL), was not associated with reduction of markers of central cholinergic neurons as well as decrements in cognitive performance after chronic exposure. We compared the effect of 45 day chronic exposure of HAL (2 mg/kg per day) to OLZ (10 mg/kg per day) on brain-derived neurotrophic factor (BDNF)) and its high affinity receptor TrkB in rat hippocampus. Since the use of OLZ is presently preferred over HAL in patients, effects of its post-treatment on HAL-induced changes in the expression of BDNF and its TrkB receptor were also investigated. OLZ was administered after 45 days of HAL exposure. HAL, but not OLZ, significantly reduced the levels of BDNF in hippocampus. These changes in BDNF paralleled the levels of TrkB receptors. Furthermore, post-treatment with OLZ markedly restored the HAL treatment associated reductions in both BDNF and TrkB receptors in hippocampus.