Antipsychotic drugs clozapine and olanzapine upregulate bcl-2 mRNA and protein in rat frontal cortex and hippocampus

Brain Res. 2004 Jun 4;1010(1-2):81-6. doi: 10.1016/j.brainres.2004.02.064.

Abstract

To investigate whether atypical antipsychotic drugs exert an effect on the neuroprotective protein Bcl-2, rats were chronically treated with clozapine or olanzapine for 28 days. The expression of bcl-2 mRNA and Bcl-2 protein was determined, respectively, by in situ hybridization in tissue sections and Western blot on tissue samples from rat frontal cortex and hippocampus. The bcl-2 mRNA positive cells were increased in these regions after drug treatments, and quantitative analysis revealed that the upregulation of bcl-2 mRNA and Bcl-2 protein is significantly greater than in vehicle control (p<0.05 or p<0.01). It is demonstrated that neuroprotective protein Bcl-2 is involved in the action of atypical antipsychotic drugs, and might represent a neuroprotective mechanism of these drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Benzodiazepines / pharmacology
  • Brain / drug effects*
  • Brain / metabolism
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Clozapine / pharmacology
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Neuroprotective Agents / pharmacology*
  • Olanzapine
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Up-Regulation / drug effects*
  • Up-Regulation / physiology

Substances

  • Antipsychotic Agents
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Benzodiazepines
  • Clozapine
  • Olanzapine