These authors equally contributed to this study.
Chronic social defeat up-regulates expression of the serotonin transporter in rat dorsal raphe nucleus and projection regions in a glucocorticoid-dependent manner
Article first published online: 7 NOV 2012
© 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 123, Issue 6, pages 1054–1068, December 2012
How to Cite
J. Neurochem. (2012) 123, 1054–1068.
- Issue published online: 4 DEC 2012
- Article first published online: 7 NOV 2012
- Accepted manuscript online: 13 OCT 2012 08:25AM EST
- Manuscript Accepted: 2 OCT 2012
- Manuscript Revised: 27 SEP 2012
- Manuscript Received: 10 AUG 2012
- NIH. Grant Number: MH080323
- chronic social defeat;
- corticosteroid receptors;
- raphe nuclei;
- rat brain;
- serotonin transporter
Chronic stress and dysfunction of the serotonergic system in the brain have been considered two of the major risks for development of depression. In this study, adult Fischer 344 rats were subjected to a regimen of chronic social defeat (CSD). To mimic stressful conditions, some rats were not exposed to CSD, but instead treated with corticosterone (CORT) in oral solution while maintained in their home cage. Protein levels of the serotonin transporter (SERT) in the dorsal raphe nucleus (DRN), hippocampus, frontal cortex, and amygdala were examined by Western blotting or immunofluorescence staining. The results showed that CSD up-regulated SERT protein levels in the DRN, hippocampus, frontal cortex, and amygdala regions. This up-regulation was abolished or prevented by adrenalectomy, or treatment with antagonists of corticosteroid receptors mifepristone and spironolactone, alone or in combination. Similarly, up-regulated SERT protein levels in these brain regions were also observed in rats treated with oral CORT ingestion, which was analogously prevented by treatment with mifepristone and spironolactone. Furthermore, both CSD- and CORT-induced up-regulation of SERT protein levels in the DRN and three brain regions were attenuated by simultaneous treatment with fluoxetine, an antidepressant that specifically inhibits serotonin reuptake. The results indicate that up-regulation in SERT protein levels in the DRN and forebrain limbic structures caused by CSD regimen was mainly motivated by CORT through corticosteroid receptors. The present findings demonstrate that chronic stress is closely correlated with the serotonergic system by acting on the regulation of the SERT expression in the DRN and its projection regions, which may contribute to the development of depression.