Yan Fan and Ping Chen contributed equally to this work.
Effects of chronic social defeat on expression of dopamine β-hydroxylase in rat brains
Article first published online: 5 MAR 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 67, Issue 6, pages 300–312, June 2013
How to Cite
Fan, Y., Chen, P., Li, Y. and Zhu, M.-Y. (2013), Effects of chronic social defeat on expression of dopamine β-hydroxylase in rat brains. Synapse, 67: 300–312. doi: 10.1002/syn.21641
- Issue published online: 17 APR 2013
- Article first published online: 5 MAR 2013
- Accepted manuscript online: 7 FEB 2013 06:15AM EST
- Manuscript Accepted: 29 JAN 2013
- Manuscript Received: 15 NOV 2012
- NIH . Grant Number: MH080323
- locus coeruleus;
- stress related disorders;
It is documented that stress activates the locus coeruleus-norepinephrine system. However, there are far few reports regarding effects of stress on the expression of dopamine β-hydroxylase, a hallmark enzyme of the noradrenergic neuron. In the present study, adult Fischer 344 rats were subjected to chronic social defeat for 4 weeks. Dopamine β-hydroxylase expressional levels in the locus coeruleus and its terminal regions were measured by in situ hybridization and western blotting. The results showed that immediately following chronic social defeat there are significantly increased mRNA and protein levels of dopamine β-hydroxylase in the locus coeruleus, and dopamine β-hydroxylase protein levels in the hippocampus, frontal cortex and amygdala, compared with those in the control. This chronic social defeat-induced upregulation of dopamine β-hydroxylase was completely abolished by adrenalectomy, and/or by treatment with corticosteroid receptor antagonists, mifepristone and spironolactone, either alone or in combination. Furthermore, treatment with desipramine, an antidepressant with specific inhibitory effects on norepinephrine transport, prevented an increased dopamine β-hydroxylase expression by chronic social defeat in the locus coeruleus and its main terminal regions such as the hippocampus, frontal cortex and amygdala. However, treatment with fluoxetine, an antidepressant with specific inhibition for serotonin transport, only selectively blocked increased dopamine β-hydroxylase protein levels in the hippocampus caused by CSD. The present findings indicate that chronic social defeat activates the locus coeruleus-norepinephrine system by upregulating the expression of dopamine β-hydroxylase, which may increase norepinephrine synthesis. This chronic social defeat induced upregulation of DBH expression was mediated through corticosterone and corticosteroid receptors, with possible interference from antidepressants. Synapse, 2013. © 2013 Wiley Periodicals, Inc.