Effects of chronic social defeat on expression of dopamine β‐hydroxylase in rat brains
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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.
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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 and primates.
“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 rats83–85 and primates86.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [85]
The Discussion (page not provided) reports increased dopamine β-hydroxylase (DBH) in the locus coeruleus and its terminal regions after chronic social defeat in rats. It discusses increased tyrosine hydroxylase (TH) expression but identifies the authors’ TH finding as unpublished; it also says increased norepinephrine synthesis may result, rather than measuring exaggerated norepinephrine actions. The primate finding has a separate citation in the citing sentence and is not attributed to this paper. (LLM, conf=0.85)
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The stress system in the human brain in depression and neurodegeneration
Swaab, D. F., Bao, A.-M., & Lucassen, P. J. (2005) · Ageing Research Reviews · doi:10.1016/j.arr.2005.03.003 · Cited by 984 · see citing works
Neuroendocrine pharmacology of stress
Carrasco, G. A., & Van de Kar, L. D. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01285-8 · Cited by 914 · see citing works
Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder
Southwick, S. M., Bremner, J. D., Rasmusson, A., Morgan, C. A., Arnsten, A., & Charney, D. S. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00219-x · Cited by 573 · see citing works
Abercrombie, E., & Jacobs, B. (1987) · The Journal of Neuroscience · doi:10.1523/jneurosci.07-09-02837.1987 · Cited by 377 · see citing works
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Research works printed but not linked: 69
- Armario A 2006. The hypothalamic-pituitary-adrenal axis: What can it tell us about stressors? CNS Neurol Disord Drug Targets 5: 485– 501. 17073652
- Banasr M, Valentine GW, Li XY, Gourley SL, Taylor JR, Duman RS. 2007. Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat. Biol Psychiatry 62: 496– 504. 17585885
- Baruchin A, Weisberg EP, Miner LL, Ennis D, Nisenbaum LK, Naylor E, Stricker EM, Zigmond MJ, Kaplan BB. 1990. Effects of cold exposure on rat adrenal tyrosine hydroxylase: An analysis of RNA, protein, enzyme activity, and cofactor levels. J Neurochem 54: 1769– 1775. 1691281
- Beyer CE, Boikess S, Luo B, Dawson LA. 2002. Comparison of the effects of antidepressants on norepinephrine and serotonin concentrations in the rat frontal cortex: An in-vivo microdialysis study. J Psychopharmacol 16: 297– 304. 12503828
- Biederman J, Spencer T. 1999. Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder. Biol Psychiatry 46: 1234– 1242. 10560028
- Bymaster FP, Zhang W, Carter PA, Shaw J, Chernet E, Phebus L, Wong DT, Perry KW. 2002. Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex. Psychopharmacology (Berl) 160: 353– 361. 11919662
- Charney DS. 1998. Monoamine dysfunction and the pathophysiology and treatment of depression. J Clin Psychiatry 59(Suppl 14): 11– 14. 9818625
- Chen P, Fan Y, Li Y, Sun Z, Bissette G, Zhu MY. 2012. Chronic social defeat up-regulates expression of norepinephrine transporter in rat brains. Neurochem Int 60: 9– 20. 22107703 PMC3249494
- Cryan JF, Dalvi A, Jin SH, Hirsch BR, Lucki I, Thomas SA. 2001. Use of dopamine-beta-hydroxylase-deficient mice to determine the role of norepinephrine in the mechanism of action of antidepressant drugs. J Pharmacol Exp Ther 298: 651– 657. 11454927
- Cryan JF, O’Leary OF, Jin SH, Friedland JC, Ouyang M, Hirsch BR, Page ME, Dalvi A, Thomas SA, Lucki I. 2004. Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors. Proc Natl Acad Sci USA 101: 8186– 8191. 15148402 PMC419578
- Fan Y, Huang J, Duffourc M, Kao RL, Ordway GA, Huang R, Zhu MY. 2011. Transcription factor Phox2 upregulates expression of norepinephrine transporter and dopamine beta-hydroxylase in adult rat brains. Neuroscience 192: 37– 53. 21763404 PMC3166407
- Frazer A 2000. Norepinephrine involvement in antidepressant action. J Clin Psychiatry 61(Suppl 10): 25– 30. 10910014
- Friedman S, Kaufman S. 1965. 3,4-Dihydroxyphenylethylamine Beta-Hydroxylase: A Copper Protein. J Biol Chem 240: PC552– PC554. 14253475
- Gavrilovic L, Spasojevic N, Dronjak S. 2009. Psychosocial stress-related changes in gene expression of norepinephrine biosynthetic enzymes in stellate ganglia of adult rats. Autonomic Neurosci 150: 144– 146. 19482560
- Glavin GB, Tanaka M, Tsuda A, Kohno Y, Hoaki Y, Nagasaki N. 1983. Regional rat brain noradrenaline turnover in response to restraint stress. Pharmacol Biochem Behav 19: 287– 290. 6685313
- Gobert A, Rivet JM, Cistarelli L, Melon C, Millan MJ. 1997. Alpha2-adrenergic receptor blockade markedly potentiates duloxetine- and fluoxetine-induced increases in noradrenaline, dopamine, and serotonin levels in the frontal cortex of freely moving rats. J Neurochem 69: 2616– 2619. 9375697
- Goddard AW, Ball SG, Martinez J, Robinson MJ, Yang CR, Russell JM, Shekhar A. 2010. Current perspectives of the roles of the central norepinephrine system in anxiety and depression. Depress Anxiety 27: 339– 350. 19960531
- Goldstein M, Fuxe K, Hokfelt T. 1972. Characterization and tissue localization of catecholamine synthesizing enzymes. Pharmacol Rev 24: 293– 309. 4564603
- Hajos-Korcsok E, McTavish SF, Sharp T. 2000. Effect of a selective 5-hydroxytryptamine reuptake inhibitor on brain extracellular noradrenaline: Microdialysis studies using paroxetine. Eur J Pharmacol 407: 101– 107. 11050296
- Haller J, Millar S, Kruk MR. 1998. Mineralocorticoid receptor blockade inhibits aggressive behaviour in male rats. Stress 2: 201– 207. 9787267
- Hashimoto K, Suemaru S, Takao T, Sugawara M, Makino S, Ota Z. 1988. Corticotropin-releasing hormone and pituitary-adrenocortical responses in chronically stressed rats. Regul Pept 23: 117– 126. 2852828
- Hauger RL, Lorang M, Irwin M, Aguilera G. 1990. CRF receptor regulation and sensitization of ACTH responses to acute ether stress during chronic intermittent immobilization stress. Brain Res 532: 34– 40. 2178035
- Hornykiewicz O 1982. Brain catecholamines in schizophrenia—A good case for noradrenaline. Nature 299: 484– 486. 7121591
- Howland JG, Wang YT. 2008. Synaptic plasticity in learning and memory: Stress effects in the hippocampus. Prog Brain Res 169: 145– 158. 18394472
- Hughes ZA, Stanford SC. 1996. Increased noradrenaline efflux induced by local infusion of fluoxetine in the rat frontal cortex. Eur J Pharmacol 317: 83– 90. 8982723
- Jordan S, Kramer GL, Zukas PK, Moeller M, Petty F. 1994. In vivo biogenic amine efflux in medial prefrontal cortex with imipramine, fluoxetine, and fluvoxamine. Synapse 18: 294– 297. 7886621
- Kim CH, Zabetian CP, Cubells JF, Cho S, Biaggioni I, Cohen BM, Robertson D, Kim KS. 2002. Mutations in the dopamine beta-hydroxylase gene are associated with human norepinephrine deficiency. Am J Med Genet 108: 140– 147. 11857564
- Kobayashi K, Morita S, Mizuguchi T, Sawada H, Yamada K, Nagatsu I, Fujita K, Nagatsu T. 1994. Functional and high level expression of human dopamine beta-hydroxylase in transgenic mice. J Biol Chem 269: 29725– 29731. 7961964
- Kovacs KJ. 1998. c-Fos as a transcription factor: A stressful (re)view from a functional map. Neurochem Int 33: 287– 297. 9840219
- Kubovcakova L, Tybitanclova K, Sabban EL, Majzoub J, Zorad S, Vietor I, Wagner EF, Krizanova O, Kvetnansky R. 2004. Catecholamine synthesizing enzymes and their modulation by immobilization stress in knockout mice. Ann NY Acad Sci 1018: 458– 465. 15240402
- Kvetnansky R, Krizanova O, Tillinger A, Sabban EL, Thomas SA, Kubovcakova L. 2008. Regulation of gene expression of catecholamine biosynthetic enzymes in dopamine-beta-hydroxylase- and CRH-knockout mice exposed to stress. Ann NY Acad Sci 1148: 257– 268. 19120118 PMC4482230
- Kvetnansky R, Micutkova L, Rychkova N, Kubovcakova L, Mravec B, Filipenko M, Sabban EL, Krizanova O. 2004. Quantitative evaluation of catecholamine enzymes gene expression in adrenal medulla and sympathetic Ganglia of stressed rats. Ann NY Acad Sci 1018: 356– 369. 15240391
- Macunluoglu B, Arikan H, Atakan A, Tuglular S, Ulfer G, Cakalagaoglu F, Ozener C, Akoglu E. 2008. Effects of spironolactone in an experimental model of chronic cyclosporine nephrotoxicity. Transplant Proc 40: 273– 278. 18261605
- McDougall SJ, Widdop RE, Lawrence AJ. 2005. Differential gene expression in WKY and SHR brain following acute and chronic air-puff stress. Brain Res Mol Brain Res 133: 329– 336. 15710252
- McMahon A, Sabban EL. 1992. Regulation of expression of dopamine beta-hydroxylase in PC12 cells by glucocorticoids and cyclic AMP analogues. J Neurochem 59: 2040– 2047. 1359011
- Melia KR, Duman RS. 1991. Involvement of corticotropin-releasing factor in chronic stress regulation of the brain noradrenergic system. Proc Natl Acad Sci USA 88: 8382– 8386. 1681536 PMC52512
- Melia KR, Nestler EJ, Duman RS. 1992. Chronic imipramine treatment normalizes levels of tyrosine hydroxylase in the locus coeruleus of chronically stressed rats. Psychopharmacology (Berl) 108: 23– 26. 1357707
- Nagatsu T 1986. Neurotransmitter Enzymes: Neuromethods. Humana Press, Clifton, NJ.
- Nankova B, Kvetnansky R, McMahon A, Viskupic E, Hiremagalur B, Frankle G, Fukuhara K, Kopin IJ, Sabban EL. 1994. Induction of tyrosine hydroxylase gene expression by a nonneuronal nonpituitary-mediated mechanism in immobilization stress. Proc Natl Acad Sci USA 91: 5937– 5941. 7912437 PMC44112
- Nankova BB, Tank AW, Sabban EL. 1999. Transient or sustained transcriptional activation of the genes encoding rat adrenomedullary catecholamine biosynthetic enzymes by different durations of immobilization stress. Neuroscience 94: 803– 808. 10579571
- Nestler EJ, Alreja M, Aghajanian GK. 1999. Molecular control of locus coeruleus neurotransmission. Biol Psychiatry 46: 1131– 1139. 10560020
- Ni H, Mune T, Morita H, Daidoh H, Hanafusa J, Shibata T, Yamakita N, Yasuda K. 1995. Inhibition of aldosterone turn-off phenomenon following chronic adrenocorticotropin treatment with in vivo administration of antiglucocorticoid and antioxidants in rats. Eur J Endocrinol 133: 578– 584. 7581988
- Ohlstein EH, Kruse LI, Ezekiel M, Sherman SS, Erickson R, DeW-olf WE Jr, Berkowitz BA. 1987. Cardiovascular effects of a new potent dopamine beta-hydroxylase inhibitor in spontaneously hypertensive rats. J Pharmacol Exp Ther 241: 554– 559. 3572812
- Pacak K, Palkovits M, Kopin IJ, Goldstein DS. 1995. Stress-induced norepinephrine release in the hypothalamic paraventricular nucleus and pituitary-adrenocortical and sympathoadrenal activity: In vivo microdialysis studies. Front Neuroendocrinol 16: 89– 150. 7621982
- Pace TW, Gaylord RI, Jarvis E, Girotti M, Spencer RL. 2009. Differential glucocorticoid effects on stress-induced gene expression in the paraventricular nucleus of the hypothalamus and ACTH secretion in the rat. Stress 12: 400– 411. 19065454 PMC2787849
- Papp M, Willner P, Muscat R. 1991. An animal model of anhedonia: Attenuation of sucrose consumption and place preference conditioning by chronic unpredictable mild stress. Psychopharmacology (Berl) 104: 255– 259. 1876670
- Paxinos G, Watson C. 2005. The rat brain in stereotaxic coordinates. Oxford, UK: Elsevier. 6110810
- Perry KW, Fuller RW. 1997. Fluoxetine increases norepinephrine release in rat hypothalamus as measured by tissue levels of MHPG-SO4 and microdialysis in conscious rats. J Neural Transm 104: 953– 966. 9451727
- Ratka A, Sutanto W, Bloemers M, de Kloet ER. 1989. On the role of brain mineralocorticoid (type I) and glucocorticoid (type II) receptors in neuroendocrine regulation. Neuroendocrinology 50: 117– 123. 2550833
- Recamier-Carballo S, Estrada-Camarena E, Reyes R, Fernandez-Guasti A. 2012. Synergistic effect of estradiol and fluoxetine in young adult and middle-aged female rats in two models of experimental depression. Behav Brain Res 233: 351– 358. 22652396
- Robbins T, Everitt B. 1995. Central norepinephrine neurons and behavior. In: Bloom F, Kupfer D, editors. Neuropsychopharmacology: The fourth generation of progress. New York: Raven Press.
- Rygula R, Abumaria N, Domenici E, Hiemke C, Fuchs E. 2006. Effects of fluoxetine on behavioral deficits evoked by chronic social stress in rats. Behav Brain Res 174: 188– 192. 16949682
- Rygula R, Abumaria N, Flugge G, Fuchs E, Ruther E, Havemann-Reinecke U. 2005. Anhedonia and motivational deficits in rats: Impact of chronic social stress. Behav Brain Res 162: 127– 134. 15922073
- Sabban EL. 2007. Catecholamines in stress: Molecular mechanisms of gene expression. Endocr Regul 41: 61– 73. 18257649
- Sabban EL, Kvetnansky R. 2001. Stress-triggered activation of gene expression in catecholaminergic systems: Dynamics of transcriptional events. Trends Neurosci 24: 91– 98. 11164939
- Serova LI, Nankova BB, Feng Z, Hong JS, Hutt M, Sabban EL. 1999. Heightened transcription for enzymes involved in norepinephrine biosynthesis in the rat locus coeruleus by immobilization stress. Biol Psychiatry 45: 853– 862. 10202573
- Smagin GN, Zhou J, Harris RB, Ryan DH. 1997. CRF receptor antagonist attenuates immobilization stress-induced norepinephrine release in the prefrontal cortex in rats. Brain Res Bull 42: 431– 434. 9128917
- Smith MA, Brady LS, Glowa J, Gold PW, Herkenham M. 1991. Effects of stress and adrenalectomy on tyrosine hydroxylase mRNA levels in the locus ceruleus by in situ hybridization. Brain Res 544: 26– 32. 1677301
- Spasojevic N, Gavrilovic L, Dronjak S. 2010. Effects of repeated maprotiline and fluoxetine treatment on gene expression of catecholamine synthesizing enzymes in adrenal medulla of unstressed and stressed rats. Autonomic Autacoid Pharmacol 30: 213– 217. 20626387
- Thomas DN, Nutt DJ, Holman RB. 1998. Sertraline, a selective serotonin reuptake inhibitor modulates extracellular noradrenaline in the rat frontal cortex. J Psychopharmacol 12: 366– 370. 10065910
- Udenfriend S 1966. Tyrosine hydroxylase. Pharmacol Rev 18: 43– 51. 5904159
- Usher M, Cohen JD, Servan-Schreiber D, Rajkowski J, Aston-Jones G. 1999. The role of locus coeruleus in the regulation of cognitive performance. Science 283: 549– 554. 9915705
- Watanabe Y, McKittrick CR, Blanchard DC, Blanchard RJ, McEwen BS, Sakai RR. 1995. Effects of chronic social stress on tyrosine hydroxylase mRNA and protein levels. Brain Res Mol Brain Res 32: 176– 180. 7494459
- Wong DL, Wang W. 1994. Neural control of dopamine beta-hydroxylase in vivo: Acute and chronic effects. Brain Res Mol Brain Res 25: 57– 66. 7984052
- Yang C, Wang G, Wang H, Liu Z, Wang X. 2009. Cytoskeletal alterations in rat hippocampus following chronic unpredictable mild stress and re-exposure to acute and chronic unpredictable mild stress. Behav Brain Res 205: 518– 524. 19683020
- Zhang W, Perry KW, Wong DT, Potts BD, Bao J, Tollefson GD, Bymaster FP. 2000. Synergistic effects of olanzapine and other antipsychotic agents in combination with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex. Neuropsychopharmacology 23: 250– 262. 10942849
- Zhu MY, Kim CH, Hwang DY, Baldessarini RJ, Kim KS. 2002. Effects of desipramine treatment on norepinephrine transporter gene expression in the cultured SK-N-BE(2)M17 cells and rat brain tissue. J Neurochem 82: 146– 153. 12091475
- Zhu MY, Wang WP, Baldessarini RJ, Kim KS. 2005. Effects of desipramine treatment on tyrosine hydroxylase gene expression in cultured neuroblastoma cells and rat brain tissue. Brain Res Mol Brain Res 133: 167– 175. 15710233
- Zigmond RE, Schon F, Iversen LL. 1974. Increased tyrosine hydroxylase activity in the locus coeruleus of rat brain stem after reserpine treatment and cold stress. Brain Res 70: 547– 552. 4150707
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- Authors
- Fan, Y., Chen, P., Li, Y., & Zhu, M.
- Affiliations
- East Tennessee State University (US)
- Tongji University (CN)
- Corresponding author
- Zhu, Meng‐Yang
- Venue
- Synapse
- Publisher
- Wiley
- Published
- 2013-03-05
- Volume
- 67
- Issue
- 6
- Pages
- 300-312
- ISSN
- 0887-4476 (ISSN-L)
- 1098-2396
- PMC
- PMC9338777
- OpenAlex
- W1786343825
- Cited by
- 36
- References
- 4
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 2 · 2013: 1
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Synapse (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons - East Tennessee State University (East Tennessee State University) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH080323, MH080323)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- chronic social defeat, dopamine beta-hydroxylase, locus coeruleus, noradrenergic system, stress, corticosterone, corticosteroid receptors, adrenalectomy, mifepristone, spironolactone, desipramine, fluoxetine, hippocampus, amygdala, frontal cortex, antidepressants
- MeSH terms
- Adrenalectomy, Mineralocorticoid Receptor Antagonists, Animals, Antidepressive Agents, Brain, Desipramine, Dopamine beta-Hydroxylase, Fluoxetine, Hormone Antagonists, Male, Rats, Inbred F344, RNA, Messenger, Social Behavior, Spironolactone, Stress, Psychological, Transcription, Genetic, Mifepristone, Up-Regulation, Rats, Long-Evans, Rats
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