Common changes in rat cortical gene expression after antidepressant drug treatment: Impacts on metabolism of polyamines, mRNA splicing, regulation of RAS by GAPs, neddylation and GPCR ligand binding

Abstract

Objectives

This study sought to identify pathways affected by rat cortical RNA that were changed after treatment with fluoxetine or imipramine.

Methods

We measured levels of cortical RNA in male rats using GeneChip^® Rat Exon 1.0 ST Array after treatment with vehicle (0.9% NaCl), fluoxetine (10 mg/kg/day) or imipramine (20 mg/kg/day) for 28 days. Levels of coding and non-coding RNA in vehicle treated rats were compared to those in treated rats using ANOVA in JMP Genomics 13 and the Panther Gene Ontology Classification System was used to identify pathways involving the changed RNAs.

Results

18,876 transcripts were detected; there were highly correlated changes in 1010 levels of RNA after both drug treatments that would principally affect the metabolism of polyamines, mRNA splicing, regulation of RAS by GAPs, neddylation and GPCR ligand binding. Using our previously published data, we compared changes in transcripts after treatment with antipsychotic and mood stabilising drugs.

Conclusions

Our study shows there are common, correlated, changes in coding and non-coding RNA in the rat cortex after treatment with fluoxetine or imipramine; we propose the pathways affected by these changes are involved in the therapeutic mechanisms of action of antidepressant drugs.

Keywords:

• Rat
• cortex
• transcriptome
• fluoxetine
• imipramine

Acknowledgements

None.

Statement of interest

None to declare.

Additional information

Funding

This work was supported by the CRC for Mental Health and the Operational Infrastructure Support from the Victorian State Government.