Chronic atypical antipsychotics, but not haloperidol, increase neurogenesis in the hippocampus of adult mouse

Brain Res. 2017 Dec 1:1676:77-82. doi: 10.1016/j.brainres.2017.09.006. Epub 2017 Sep 9.

Abstract

It is suggested that altered neuroplasticity contributes to the pathophysiology of schizophrenia and antipsychotics may exhibit some of their therapeutic efficacies by improving neurogenesis and/or proliferation of neural progenitors. The aim of this study is to investigate whether chronic antipsychotics treatment affect neurogenesis in adult mouse hippocampus. Animals were administered olanzapine, quetiapine, clozapine, risperidone, aripiprazole, or haloperidol via the osmotic minipump for 21days and then injected with 5-bromo-2'-deoxyuridine (BrdU) to label mitotic cells. BrdU-positive cells in the hippocampus were quantified by stereology. Aripiprazole, quetiapine, clozapine, and olanzapine significantly increased density of BrdU-positive cells in the hippocampus. Interestingly, other antipsychotic drugs had tendency to increasing BrdU-positive cells, whereas haloperidol had propensity to decrease with a marginal significance. These results suggest that differences of neurogenesis among these drugs may, at least in part, account for their pharmacological profiles.

Keywords: 5-bromo-2′-deoxyuridine (BrdU); Antipsychotics; Hippocampus; Mouse; Neurogenesis; Schizophrenia.

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Aripiprazole / pharmacology
  • Benzodiazepines / pharmacology
  • Bromodeoxyuridine
  • Cell Count
  • Clozapine / pharmacology
  • Haloperidol / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Immunohistochemistry
  • Male
  • Mice, Inbred C57BL
  • Neurogenesis / drug effects*
  • Neurons / drug effects
  • Neurons / pathology
  • Olanzapine
  • Quetiapine Fumarate / pharmacology

Substances

  • Antipsychotic Agents
  • Benzodiazepines
  • Quetiapine Fumarate
  • Aripiprazole
  • Bromodeoxyuridine
  • Clozapine
  • Haloperidol
  • Olanzapine