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

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. Copyright 2004 Elsevier B.V.