Downregulation of Ccnd1 and Hes6 in rat hippocampus after chronic exposure to the antidepressant paroxetine.
OBJECTIVE
The mechanism of action of antidepressant drugs is not fully understood. Application of genomic methods enables the identification of biochemical pathways that are regulated by antidepressants, and this may provide novel clues to the molecular and cellular actions of these drugs. The present study examined gene expression profiles in the hippocampus of rats exposed to chronic antidepressant treatment.


METHODS
Animals were treated for 12 days with the selective serotonin reuptake inhibitor paroxetine; then, hippocampal ribonucleic acid was recovered, and changes in gene expression were assessed by microarray analysis.


RESULTS
A total of 160 genes that showed differential expression after paroxetine exposure were identified. Using functional relevance and observed fold change as selection criteria, the expression changes in a subset of these genes were confirmed by quantitative polymerase chain reaction.


CONCLUSIONS
Of this subset, only two genes, cyclin D1 (Ccnd1) and hairy and enhancer of split 6 (Hes6), showed robust and consistent changes in expression. Both genes were downregulated by paroxetine, and both have been previously implicated in neurogenesis. Further investigation of these two genes may provide new insight into the mechanism of action of antidepressants.
1Department of Pathology, University of Otago, Christchurch, Christchurch, New Zealand.
Patrick C
PC
McHugh
1Department of Pathology, University of Otago, Christchurch, Christchurch, New Zealand.
Geraldine R
GR
Rogers
1Department of Pathology, University of Otago, Christchurch, Christchurch, New Zealand.
Dylan M
DM
Glubb
1Department of Pathology, University of Otago, Christchurch, Christchurch, New Zealand.
Melanie D
MD
Allington
2Genetics Factors, Riccarton, Christchurch, New Zealand.
Mark
M
Hughes
3Department of Psychological Medicine, University of Otago, Christchurch, Christchurch, New Zealand.
Peter R
PR
Joyce
1Department of Pathology, University of Otago, Christchurch, Christchurch, New Zealand.
Martin A
MA
Kennedy