Effects of chronic social defeat on expression of dopamine β‐hydroxylase in rat brains

Abstract

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.

Corticosterone administration up‐regulated expression of norepinephrine transporter and dopamine β‐hydroxylase in rat locus coeruleus and its terminal regions

“…) and DBH (Fan et al . ) in the LC and its main projection regions, indicating that chronic stress activated the noradrenergic system by action on noradrenergic phenotypes. To further clarify this relationship, this study was carried out through oral administration of CORT to mimic the chronic stress.…”

“…Furthermore, CSD also increased the expression of DBH in the same brain regions (Fan et al . ). To further verify that CORT secreted during stressful events accounts for this effect, adult Fischer 344 rats were treated with a dose relevant to stress‐induced plasma CORT concentration, and the expression of NET and DBH in the LC as well as the main NE terminal regions were examined.…”

Stress weakens prefrontal networks: molecular insults to higher cognition

“…The actions of norepinephrine are exaggerated with chronic stress exposure: there is increased expression of the synthetic enzymes tyrosine hydroxylase and dopamine β-hydroxylase in noradrenergic neurons and axons in both rats 83–85 and primates 86 . Chronic stress also increases the tonic firing of locus coeruleus neurons via increased CRF–PKA activation of pacemaker cation channels 87 .…”

Effects of Estradiol Valerate and Remifemin on Norepinephrine Signaling in the Brain of Ovariectomized Rats

“…Dopamine β-hydroxylase (DBH, an enzyme marker for noradrenaline synthesis) [21] was used to label norepinephrinergic fibers and neurons in the POAH and LC, respectively. Mouse anti-DBH monoclonal antibody (1:700; MAB308, Millipore, Billerica, Mass., USA), rabbit anti-ERα polyclonal antibody (1:200, SC-542, Santa Cruz Biotechnology, Santa Cruz, Calif., USA), and the avidin-biotin complex labeling kits (SP-9001, SP-9002, PV 6002, Beijing Zhongshan Goldenbridge Biotechnology Co., Ltd., Beijing, PR China) were used for immunohistochemistry.…”

“…It is a key enzyme for norepinephrine synthesis and is widely used as a marker for norepinephrine [21]. In this study, DBH was labeled to mark norepinephrine fibers in the POAH and neurons in the LC.…”