title: Inactivation of glucocorticoid receptor in noradrenergic system influences anxiety- and depressive-like behavior in mice.
abstract: The aim of this study was to investigate whether conditional inactivation of the glucocorticoid receptors (GRs) in noradrenergic neurons affects animal behavior in mice. Selective ablation of GRs in the noradrenergic system was achieved using the Cre/loxP approach. We crossed transgenic mice expressing the Cre recombinase under the dopamine beta-hydroxylase (DBH) promoter with animals harboring the floxed GR gene. The resulting GR(DBHCre) mutant mice exhibited no alterations in terms of normal cage behavior, weight gain, spatial memory or spontaneous locomotor activity, regardless of gender. To assess depressive- and anxiety-like behaviors we performed the Tail Suspension Test and the Light-Dark Box Test. While male mutant animals did not show any alternations in both tests, female GR(DBHCre) mutants displayed depressive- and anxiety-like behavior. Additionally, male GR(DBHCre) mice were exposed to chronic restraint stress but still exhibited immobility times and anxiety statuses similar to those of non-stressed animals while stressed control mice clearly revealed depressive- and anxiety-like phenotype. Thus, in males the effects of the mutation were precipitated only after chronic restraint stress procedure. Our data reveal a possible gender-dependent role of GRs in the noradrenergic system in anxiety- and depressive-like behavior in mice.
authors: Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.
authors: Piotr
authors: P
authors: Chmielarz
authors: Justyna
authors: J
authors: Kuśmierczyk
authors: Rosanna
authors: R
authors: Parlato
authors: Günther
authors: G
authors: Schütz
authors: Irena
authors: I
authors: Nalepa
authors: Grzegorz
authors: G
authors: Kreiner
mesh_terms: D059331:Adrenergic Neurons / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001008:Anxiety Disorders / Q000097:blood / Q000378:metabolism* / Q000523:psychology; D001522:Behavior, Animal; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000097:blood / Q000378:metabolism* / Q000523:psychology; D005260:Female; D008125:Locus Coeruleus / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D011965:Receptors, Glucocorticoid; D003345:Corticosterone
references: Development. 2007 May;134(9):1663-70
references: 17376811
references: Neuropharmacology. 1983 Sep;22(9):1055-60
references: 6314168
references: Brain Res. 2002 Jul 12;943(2):216-23
references: 12101044
references: J Neurochem. 2010 Apr;113(1):105-16
references: 20070865
references: Physiol Rev. 2009 Apr;89(2):535-606
references: 19342614
references: Psychopharmacology (Berl). 1990;101(1):27-33
references: 2343073
references: Eur J Neurosci. 2008 May;27(9):2433-43
references: 18461718
references: Pharmacol Biochem Behav. 2006 Oct;85(2):332-8
references: 17049370
references: Eur J Pharmacol. 2003 Feb 28;463(1-3):55-65
references: 12600702
references: Neuroscience. 2005;135(3):703-14
references: 16125862
references: Curr Opin Genet Dev. 1998 Oct;8(5):532-8
references: 9794823
references: Brain Res. 1986 Mar 19;368(2):404-8
references: 3008931
references: Behav Brain Res. 2011 Jun 20;220(1):106-11
references: 21277333
references: Pharmacol Rep. 2012;64(5):1066-80
references: 23238464
references: Neuropsychopharmacology. 2000 Nov;23(5):477-501
references: 11027914
references: J Neurosci. 1985 May;5(5):1300-6
references: 3998823
references: Neuropharmacology. 2002 Dec;43(7):1139-47
references: 12504920
references: Basic Clin Pharmacol Toxicol. 2010 Mar;106(3):226-33
references: 20050844
references: Endocrinology. 2009 Apr;150(4):1775-81
references: 19036879
references: Nat Rev Neurosci. 2005 Jun;6(6):463-75
references: 15891777
references: Brain Res Rev. 2008 Mar;57(2):554-60
references: 17524489
references: Neurosci Lett. 2009 Sep 18;461(2):121-5
references: 19539719
references: Prog Neuropsychopharmacol Biol Psychiatry. 1992 Jan;16(1):117-25
references: 1557503
references: J Neurosci. 2005 Jun 29;25(26):6243-50
references: 15987954
references: Biol Psychiatry. 1999 Nov 1;46(9):1309-20
references: 10560036
references: Histochemistry. 1986;85(2):95-106
references: 2875047
references: Sci STKE. 2004 Mar 16;2004(225):re5
references: 15039492
references: Prog Brain Res. 2000;122:25-34
references: 10737048
references: Brain Res Bull. 2002 Jul;58(3):279-84
references: 12128153
references: Naunyn Schmiedebergs Arch Pharmacol. 1996 Aug-Sep;354(3):379-83
references: 8878071