title: Estrogen receptor beta activation prevents glucocorticoid receptor-dependent effects of the central nucleus of the amygdala on behavior and neuroendocrine function.
abstract: Neuropsychiatric disorders such as anxiety and depression have formidable economic and societal impacts. A dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis leading to elevated endogenous glucocorticoid levels is often associated with such disorders. Chronically high glucocorticoid levels may act upon the central nucleus of the amygdala (CeA) to alter normally adaptive responses into those that are maladaptive and detrimental. In addition to glucocorticoids, other steroid hormones such as estradiol and androgens can also modify hormonal and behavioral responses to threatening stimuli. In particular, estrogen receptor beta (ERbeta) agonists have been shown to be anxiolytic. Consequently, these experiments addressed the hypothesis that the selective stimulation of glucocorticoid receptor (GR) in the CeA would increase anxiety-like behaviors and HPA axis reactivity to stress, and further, that an ERbeta agonist could modulate these effects. Young adult female Sprague-Dawley rats were ovariectomized and bilaterally implanted via stereotaxic surgery with a wax pellet containing the selective GR agonist RU28362 or a blank pellet, to a region just dorsal to the CeA. Four days later, animals were administered the ERbeta agonist S-DPN or vehicle (with four daily sc injections). Anxiety-type behaviors were measured using the elevated plus maze (EPM). Central RU28362 implants caused significantly higher anxiety-type behaviors in the EPM and greater plasma CORT levels than controls given a blank central implant. Moreover, S-DPN treated animals, regardless of type of central implant, displayed significantly lower anxiety-type behaviors and post-EPM plasma CORT levels than vehicle treated controls or vehicle treated animals implanted with RU28362. These results indicate that selective activation of GR within the CeA is anxiogenic, and peripheral administration of an ERbeta agonist can overcome this effect. These data suggest that estradiol signaling via ERbeta prevents glucocorticoid-dependent effects of the CeA on behavior and neuroendocrine function.
authors.affiliation: Department of Biomedical Sciences, Neuroscience Division, Colorado State University, Fort Collins, CO, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weiser
authors.forename: Chad D
authors.initials: CD
authors.lastname: Foradori
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Handa
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D045166:Estradiol Congeners / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D009490:Neurosecretory Systems / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013315:Stress, Psychological
chemical_list: D045166:Estradiol Congeners; D047629:Estrogen Receptor beta; D011965:Receptors, Glucocorticoid
references.citation: Endocrinology. 2005 Feb;146(2):797-807
references.pmid: 15514081
references.citation: Neuroendocrinology. 1993 Mar;57(3):517-24
references.pmid: 8391664
references.citation: Neuroscience. 1998 Sep;86(2):449-59
references.pmid: 9881860
references.citation: Annu Rev Neurosci. 1992;15:353-75
references.pmid: 1575447
references.citation: Brain Res. 1995 Feb 13;671(2):213-21
references.pmid: 7743210
references.citation: Psychoneuroendocrinology. 2008 Jul;33(6):773-81
references.pmid: 18407426
references.citation: Behav Brain Res. 2005 Jun 3;161(1):39-44
references.pmid: 15904708
references.citation: J Comp Neurol. 2006 Dec 20;499(6):911-23
references.pmid: 17072840
references.citation: Mol Endocrinol. 1990 Oct;4(10):1427-37
references.pmid: 1704480
references.citation: Front Neuroendocrinol. 2003 Jul;24(3):151-80
references.pmid: 14596810
references.citation: Eur J Pharmacol. 2008 Apr 7;583(2-3):255-62
references.pmid: 18339373
references.citation: Neuroscience. 1998 Jul;85(1):135-47
references.pmid: 9607709
references.citation: J Neuroendocrinol. 2004 Mar;16(3):272-8
references.pmid: 15049858
references.citation: Ann N Y Acad Sci. 1994 Nov 30;746:438-40
references.pmid: 7825910
references.citation: J Neuropsychiatry Clin Neurosci. 1997 Summer;9(3):382-402
references.pmid: 9276841
references.citation: Stress. 2002 Dec;5(4):235-47
references.pmid: 12475728
references.citation: J Comp Neurol. 1980 Nov 1;194(1):267-89
references.pmid: 7440798
references.citation: J Comp Neurol. 2001 Jul 16;436(1):64-81
references.pmid: 11413547
references.citation: Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12278-82
references.pmid: 11593044
references.citation: J Neuroendocrinol. 1994 Aug;6(4):433-42
references.pmid: 7987374
references.citation: J Biol Chem. 1983 Jan 10;258(1):417-25
references.pmid: 6848510
references.citation: J Comp Neurol. 1992 Oct 8;324(2):180-94
references.pmid: 1430328
references.citation: Neuroscience. 1998 Jun;84(4):1025-39
references.pmid: 9578393
references.citation: Eur J Neurol. 2007 Feb;14(2):e9
references.pmid: 17250716
references.citation: Exp Physiol. 1997 Mar;82(2):273-81
references.pmid: 9129941
references.citation: Brain Res Rev. 2008 Mar;57(2):309-20
references.pmid: 17662459
references.citation: Neurosci Res. 1996 Nov;26(3):235-69
references.pmid: 9121734
references.citation: Annu Rev Neurosci. 2004;27:193-222
references.pmid: 15217331
references.citation: Nature. 1986 Mar 13-19;320(6058):134-9
references.pmid: 3754034
references.citation: Pharmacol Biochem Behav. 2007 Feb;86(2):407-14
references.pmid: 16916539
references.citation: Horm Behav. 1994 Dec;28(4):464-76
references.pmid: 7729815
references.citation: Biol Psychol. 2001 Jul-Aug;57(1-3):141-52
references.pmid: 11454437
references.citation: Metabolism. 2005 May;54(5 Suppl 1):20-3
references.pmid: 15877308
references.citation: Physiol Rev. 2003 Jul;83(3):803-34
references.pmid: 12843409
references.citation: J Comp Neurol. 2005 Mar 28;484(1):28-42
references.pmid: 15717309
references.citation: J Neurosci Methods. 1985 Aug;14(3):149-67
references.pmid: 2864480
references.citation: Brain Res. 1994 Sep 26;658(1-2):21-6
references.pmid: 7834344
references.citation: J Pharmacol Toxicol Methods. 1993 Jun;29(3):129-38
references.pmid: 8103377
references.citation: Physiol Behav. 2005 Jan 31;84(1):157-63
references.pmid: 15642619
references.citation: J Neuroendocrinol. 2001 May;13(5):442-52
references.pmid: 11328455
references.citation: Endocrinology. 1985 Dec;117(6):2505-11
references.pmid: 2998738
references.citation: Brain Res Bull. 1994;35(4):379-82
references.pmid: 7850490
references.citation: Epidemiol Psichiatr Soc. 2009 Jan-Mar;18(1):23-33
references.pmid: 19378696
references.citation: Mol Endocrinol. 1996 Oct;10(10):1191-205
references.pmid: 9121487
references.citation: Neuroendocrinology. 1986;44(2):247-54
references.pmid: 3025760
references.citation: J Biol Chem. 1984 Jan 25;259(2):820-31
references.pmid: 6693398
references.citation: Brain Res Mol Brain Res. 1998 Feb;54(1):175-80
references.pmid: 9526077
references.citation: J Affect Disord. 2003 Mar;74(1):85-96
references.pmid: 12646301
references.citation: Brain Res. 1987 Mar 31;407(2):327-31
references.pmid: 3567648
references.citation: Behav Neurosci. 2008 Oct;122(5):974-81
references.pmid: 18823154
references.citation: Gen Pharmacol. 1990;21(1):83-7
references.pmid: 2298391
references.citation: Brain Res. 1994 Mar 21;640(1-2):105-12
references.pmid: 8004437
references.citation: Clin Exp Pharmacol Physiol. 1998 Oct;25(10):764-75
references.pmid: 9784914
references.citation: Psychoneuroendocrinology. 1996 Oct;21(7):609-20
references.pmid: 9044444
references.citation: J Comp Neurol. 1997 Dec 1;388(4):507-25
references.pmid: 9388012
references.citation: J Comp Neurol. 1989 Jul 22;285(4):413-35
references.pmid: 2569487
references.citation: Ann N Y Acad Sci. 1993 Oct 29;697:53-60
references.pmid: 8257022
references.citation: J Neurobiol. 1998 Sep 5;36(3):357-78
references.pmid: 9733072
references.citation: Horm Behav. 2004 Aug;46(2):158-64
references.pmid: 15256305
references.citation: J Comp Neurol. 2006 Jan 1;494(1):142-78
references.pmid: 16304685
references.citation: Brain Res. 2003 Feb 14;963(1-2):203-13
references.pmid: 12560126
references.citation: Brain Res. 2000 Apr 10;861(2):288-95
references.pmid: 10760490
references.citation: Physiol Behav. 1994 Feb;55(2):371-3
references.pmid: 8153180
references.citation: Brain Res. 1984 Jun 15;303(2):337-57
references.pmid: 6204716
references.citation: Science. 1954 Dec 3;120(3127):949-50
references.pmid: 13216196
references.citation: Gend Med. 2007;4 Suppl B:S178-93
references.pmid: 18156102
references.citation: J Comp Neurol. 1981 Nov 1;202(3):335-56
references.pmid: 7298902
references.citation: Neuropsychopharmacology. 2005 Sep;30(9):1598-609
references.pmid: 15798780
references.citation: Endocrinology. 2009 Apr;150(4):1817-25
references.pmid: 19074580
references.citation: Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5925-30
references.pmid: 8650195
references.citation: J Physiol. 1995 May 1;484 ( Pt 3):721-36
references.pmid: 7623287
references.citation: Pharmacol Biochem Behav. 1992 Oct;43(2):453-61
references.pmid: 1438482
references.citation: Brain Res Bull. 2007 Mar 15;71(5):466-74
references.pmid: 17259015
references.citation: Neuroscience. 2006 Sep 1;141(3):1503-15
references.pmid: 16806720
references.citation: Eur J Neurosci. 2001 Oct;14(7):1143-52
references.pmid: 11683906
references.citation: J Comp Neurol. 2004 Jan 6;468(2):277-98
references.pmid: 14648685
references.citation: Endocrinology. 1992 Sep;131(3):1261-9
references.pmid: 1324155
references.citation: Neuroendocrinology. 1989 Oct;50(4):433-46
references.pmid: 2554178
references.citation: Biol Psychiatry. 1998 Dec 15;44(12):1229-38
references.pmid: 9861466
references.citation: Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3588-92
references.pmid: 8386376
references.citation: Nat Cell Biol. 2009 Sep;11(9):1093-102
references.pmid: 19684579
references.citation: J Neurosci. 2006 Feb 1;26(5):1448-56
references.pmid: 16452668