Differential effects of antipsychotic and antidepressant drugs on neurogenic regions in rats

Increased neurogenesis in the hippocampus and subventricular zone (SVZ) of the brain of animals has been demonstrated following administration of several psychotropic medications. Such changes are thought to regenerate tissues and contribute to the beneficial effects of the medications. This study sought to determine if another neurogenic tissue, the peripheral olfactory epithelium (OE), might also exhibit changes after treatment with psychotropic medications. Young adult male rats were treated with risperidone and paliperidone, atypical antipsychotic medications; fluoxetine, a selective serotonin reuptake inhibitor (SSRI) antidepressant; and diluent control for 28 days via drinking water. Bromodeoxyuridine (BrdU) was injected to label dividing cells and positive cells were quantified in the OE, cortical SVZ, and dentate gyrus (DG) of the hippocampus. In the first of two studies, paliperidone and risperidone treatment (at 1 mg/kg/day) resulted in increased numbers over controls of BrdU positive cells in the OE. In the second study, examining OE, SVZ and DG in the same animal, paliperidone, but not risperidone or fluoxetine (0.6 mg/kg/day) resulted in increased cells in the OE and posterior SVZ. However, fluoxetine, but not paliperidone or risperidone treatment increased BrdU positive cells in the DG. These results show that psychotropic drug-induced cell proliferation occurs in the OE and parallels changes in the SVZ but not DG. Thus, the peripheral OE can serve as a proxy for certain psychotropic drug-induced actions on SVZ brain cell proliferation. This olfactory model can be employed in human research as a method to explore the neurogenesis effects of various pharmacologic treatments of neuropsychiatric disorders.

Research highlights
► Paliperidone treatment consistently increased olfactory epithelial neurogenesis
► Risperidone at high, but not low, dose increased olfactory neurogenesis
► The antidepressant, fluoxetine, did not increase olfactory neurogenesis
► Only paliperidone increased some svz neurogenesis, resembling olfactory
► Only fluoxetine, not the antipsychotics, increased hippocampal neurogenesis