Common changes in rat cortical gene expression after chronic treatment with chlorpromazine and haloperidol may be related to their antipsychotic efficacy

It has been postulated that common molecular changes resulting from treatment with antipsychotic drugs are involved in their therapeutic mechanisms of action. There are studies showing antipsychotic drug treatment causes changes in rat cortical gene expression. Hence, in this study, we sort to identify common changes in gene expression caused by two antipsychotic drugs because such changes could be related to their therapeutic mechanisms of action. In this study, RNA levels in rat cortex was measured using Affymetrix GeneChip® Rat Genome 230 2.0 Arrays after treatment with vehicle, haloperidol or chlorpromazine in drinking water for 28 days (n ​= ​10 per group). Panther Gene Ontology Classification System was used to identify biological consequences of changes in gene expression after drug treatment. Using criteria for differential gene expression established using our current data sets, compared to vehicle, chlorpromazine and haloperidol treatment changed levels of cortical RNA for 454 and 102 genes, respectively. Moreover, at the level of significance of p ​< ​0.05 treatment with both drugs cause highly correlated fold changes in the expression of 154 genes that includes enzymes and regulators of their activity, receptors and receptor signalling pathways, regulators of gene translation and transcription, components of the cytoskeleton, molecular transporters and regulators of protein trafficking across membranes. We conclude that changing gene expression is an important mechanism of action of antipsychotic drugs and some of these changes may be involved in the therapeutic benefits of those drugs.