title: 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.
authors: Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37604, USA.
authors: Yan
authors: Y
authors: Fan
authors: Ping
authors: P
authors: Chen
authors: Ying
authors: Y
authors: Li
authors: Meng-Yang
authors: MY
authors: Zhu
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003891:Desipramine / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020318:Rats, Long-Evans; D012919:Social Behavior; D013148:Spironolactone / Q000494:pharmacology; D013315:Stress, Psychological / Q000201:enzymology* / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D000928:Antidepressive Agents; D006727:Hormone Antagonists; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D005473:Fluoxetine; D013148:Spironolactone; D015735:Mifepristone; D004299:Dopamine beta-Hydroxylase; D003891:Desipramine
references: Brain Res. 1990 Nov 5;532(1-2):34-40
references: 2178035
references: J Psychopharmacol. 2002 Dec;16(4):297-304
references: 12503828
references: Brain Res. 1991 Mar 22;544(1):26-32
references: 1677301
references: Neuroendocrinology. 1989 Aug;50(2):117-23
references: 2550833
references: Pharmacol Rev. 1966 Mar;18(1):43-51
references: 5904159
references: Psychopharmacology (Berl). 2002 Apr;160(4):353-61
references: 11919662
references: Ann N Y Acad Sci. 2004 Jun;1018:356-69
references: 15240391
references: J Pharmacol Exp Ther. 2001 Aug;298(2):651-7
references: 11454927
references: Pharmacol Rev. 1972 Jun;24(2):293-309
references: 4564603
references: J Clin Psychiatry. 2000;61 Suppl 10:25-30
references: 10910014
references: Stress. 1998 Jul;2(3):201-7
references: 9787267
references: Behav Brain Res. 2006 Nov 1;174(1):188-92
references: 16949682
references: Brain Res Mol Brain Res. 1994 Aug;25(1-2):57-66
references: 7984052
references: Am J Med Genet. 2002 Mar 1;108(2):140-7
references: 11857564
references: Psychopharmacology (Berl). 1992;108(1-2):23-6
references: 1357707
references: Neuroscience. 2011 Sep 29;192:37-53
references: 21763404
references: J Neurosci. 1987 Sep;7(9):2837-43
references: 3625275
references: Neurochem Int. 1998 Oct;33(4):287-97
references: 9840219
references: Behav Brain Res. 2009 Dec 28;205(2):518-24
references: 19683020
references: J Biol Chem. 1965 Jan;240:PC552-4
references: 14253475
references: J Neural Transm (Vienna). 1997;104(8-9):953-66
references: 9451727
references: Prog Brain Res. 2008;169:145-58
references: 18394472
references: Ageing Res Rev. 2005 May;4(2):141-94
references: 15996533
references: CNS Neurol Disord Drug Targets. 2006 Oct;5(5):485-501
references: 17073652
references: Biol Psychiatry. 1999 Apr 1;45(7):853-62
references: 10202573
references: Brain Res Mol Brain Res. 1995 Aug;32(1):176-80
references: 7494459
references: Neuroscience. 1999;94(3):803-8
references: 10579571
references: Synapse. 1994 Dec;18(4):294-7
references: 7886621
references: Endocr Regul. 2007 Jun;41(2-3):61-73
references: 18257649
references: Regul Pept. 1988 Nov;23(2):117-26
references: 2852828
references: Brain Res. 1974 Apr 26;70(3):547-52
references: 4150707
references: J Neurochem. 1992 Dec;59(6):2040-7
references: 1359011
references: Trends Neurosci. 2001 Feb;24(2):91-8
references: 11164939
references: Transplant Proc. 2008 Jan-Feb;40(1):273-8
references: 18261605
references: J Neurosci Methods. 1980 Dec;3(2):129-49
references: 6110810
references: Biol Psychiatry. 1999 Nov 1;46(9):1131-9
references: 10560020
references: Auton Neurosci. 2009 Oct 5;150(1-2):144-6
references: 19482560
references: Eur J Pharmacol. 2000 Oct 27;407(1-2):101-7
references: 11050296
references: Brain Res Mol Brain Res. 2005 Feb 18;133(2):329-36
references: 15710252
references: J Neurochem. 1997 Dec;69(6):2616-9
references: 9375697
references: Brain Res Mol Brain Res. 2005 Feb 18;133(2):167-75
references: 15710233
references: Biol Psychiatry. 2007 Sep 1;62(5):496-504
references: 17585885
references: Psychopharmacology (Berl). 1991;104(2):255-9
references: 1876670
references: J Psychopharmacol. 1998;12(4):366-70
references: 10065910
references: Pharmacol Biochem Behav. 1983 Aug;19(2):287-90
references: 6685313
references: Brain Res Bull. 1997;42(6):431-4
references: 9128917
references: J Biol Chem. 1994 Nov 25;269(47):29725-31
references: 7961964
references: Stress. 2009 Sep;12(5):400-11
references: 19065454
references: Behav Brain Res. 2012 Aug 1;233(2):351-8
references: 22652396
references: Front Neuroendocrinol. 1995 Apr;16(2):89-150
references: 7621982
references: Ann N Y Acad Sci. 2008 Dec;1148:257-68
references: 19120118
references: Biol Psychiatry. 1999 Nov 1;46(9):1192-204
references: 10560025
references: Eur J Endocrinol. 1995 Nov;133(5):578-84
references: 7581988
references: Ann N Y Acad Sci. 2004 Jun;1018:458-65
references: 15240402
references: Eur J Pharmacol. 2003 Feb 28;463(1-3):235-72
references: 12600714
references: Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8382-6
references: 1681536
references: Auton Autacoid Pharmacol. 2010 Oct;30(4):213-7
references: 20626387
references: Science. 1999 Jan 22;283(5401):549-54
references: 9915705
references: Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5937-41
references: 7912437
references: Proc Natl Acad Sci U S A. 2004 May 25;101(21):8186-91
references: 15148402
references: J Clin Psychiatry. 1998;59 Suppl 14:11-4
references: 9818625
references: J Neurochem. 2002 Jul;82(1):146-53
references: 12091475
references: Nature. 1982 Oct 7;299(5883):484-6
references: 7121591
references: Biol Psychiatry. 1999 Nov 1;46(9):1234-42
references: 10560028
references: J Neurochem. 1990 May;54(5):1769-75
references: 1691281
references: Depress Anxiety. 2010 Apr;27(4):339-50
references: 19960531
references: Neuropsychopharmacology. 2000 Sep;23(3):250-62
references: 10942849
references: Behav Brain Res. 2005 Jul 1;162(1):127-34
references: 15922073
references: J Pharmacol Exp Ther. 1987 May;241(2):554-9
references: 3572812
references: Eur J Pharmacol. 1996 Dec 12;317(1):83-90
references: 8982723
references: Neurochem Int. 2012 Jan;60(1):9-20
references: 22107703