title: Chronic administration of androgens with actions at estrogen receptor beta have anti-anxiety and cognitive-enhancing effects in male rats.
abstract: Androgen levels decline with aging. Some androgens may exert anti-anxiety and cognitive-enhancing effects; however, determining which androgens have anxiolytic-like and/or mnemonic effects is of interest given the different mechanisms that may underlie some of their effects. For example, the 5 alpha-reduced metabolite of testosterone (T), dihydrotesterone, can be further converted to 5 alpha-androstane,17beta-diol-3 alpha-diol (3 alpha-diol) and 5 alpha-androstane,17beta-diol-3beta-diol (3beta-diol), both of which bind with high affinity to the beta isomer of the intracellular estrogen receptor beta (ER beta). However, androsterone, another metabolite of T, does not bind well to ER beta. To investigate the effects of T metabolites, male rats were subjected to gonadectomy then implanted with silastic capsules of 3 alpha-diol, 3beta-diol, androsterone, or oil control. After recovery, the rats were tested in elevated plus maze (EPM), light/dark transition (LD), and Morris water maze (MWM). 3 alpha-diol both decreased anxiety-like behavior in the EPM and LD, and increased cognition in MWM, while 3beta-diol improved cognition in MWM, but had no effects on anxiety behavior, compared to vehicle or androsterone. These data suggest that the actions of 3 alpha-diol and 3beta-diol at ER beta may be responsible for some of testosterone's anti-anxiety and cognitive-enhancing effects.
authors.affiliation: Department of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Osborne
authors.forename: Kassandra
authors.initials: K
authors.lastname: Edinger
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Frye
references.citation: JAMA. 2006 Nov 15;296(19):2351-61
references.pmid: 17105798
references.citation: Pharmacol Biochem Behav. 2004 Jul;78(3):523-9
references.pmid: 15251261
references.citation: Psychoneuroendocrinology. 2005 Jun;30(5):418-30
references.pmid: 15721054
references.citation: J Clin Endocrinol Metab. 1983 Jan;56(1):113-20
references.pmid: 6183286
references.citation: Horm Behav. 2006 Aug;50(2):216-22
references.pmid: 16631174
references.citation: Clin Cornerstone. 2005;7 Suppl 4:S8-12
references.pmid: 16651207
references.citation: Horm Behav. 1998 Apr;33(2):85-94
references.pmid: 9647934
references.citation: Behav Neurosci. 2004 Dec;118(6):1352-64
references.pmid: 15598144
references.citation: Neuroscience. 2006;138(3):1015-20
references.pmid: 16310318
references.citation: Psychoneuroendocrinology. 1998 May;23(4):385-99
references.pmid: 9695138
references.citation: Psychopharmacology (Berl). 2007 May;191(4):867-77
references.pmid: 17211649
references.citation: BJU Int. 2003 Aug;92(3):226-31
references.pmid: 12887472
references.citation: Cancer Res. 2005 Jun 15;65(12):5445-53
references.pmid: 15958594
references.citation: Neurobiol Learn Mem. 2007 Jan;87(1):78-85
references.pmid: 16904920
references.citation: Physiol Behav. 2007 Oct 22;92(3):443-53
references.pmid: 17544460
references.citation: Brain Res. 2002 May 10;935(1-2):73-80
references.pmid: 12062475
references.citation: Behav Brain Res. 2009 Jan 23;196(2):254-60
references.pmid: 18926853
references.citation: Horm Behav. 2008 May;53(5):741-52
references.pmid: 18067894
references.citation: Psychooncology. 2009 Mar;18(3):237-47
references.pmid: 18636420
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3996-4001
references.pmid: 11891272
references.citation: Rev Urol. 2003;5 Suppl 1:S16-21
references.pmid: 16985938
references.citation: Pharmacol Biochem Behav. 2003 May;75(2):473-9
references.pmid: 12873640
references.citation: J Neurosci Methods. 1984 May;11(1):47-60
references.pmid: 6471907
references.citation: Cogn Affect Behav Neurosci. 2001 Dec;1(4):371-81
references.pmid: 12467088
references.citation: Psychiatr Dev. 1987 Spring;5(1):1-23
references.pmid: 3601929
references.citation: Behav Brain Res. 2002 Apr 15;132(1):85-93
references.pmid: 11853861
references.citation: Mol Cell Neurosci. 1994 Dec;5(6):549-55
references.pmid: 7704428
references.citation: Pharmacol Biochem Behav. 2000 Nov;67(3):587-96
references.pmid: 11164090
references.citation: Horm Behav. 1998 Oct;34(2):126-39
references.pmid: 9799623
references.citation: Endocrinology. 1990 Feb;126(2):1165-72
references.pmid: 2298157
references.citation: Curr Drug Targets CNS Neurol Disord. 2003 Aug;2(4):233-9
references.pmid: 12871033
references.citation: J Steroid Biochem. 1983 Feb;18(2):121-5
references.pmid: 6843115
references.citation: Psychoneuroendocrinology. 2005 Sep;30(8):762-70
references.pmid: 15919582
references.citation: Horm Res. 2001;56 Suppl 1:86-92
references.pmid: 11786693
references.citation: Behav Neurosci. 2008 Oct;122(5):974-81
references.pmid: 18823154
references.citation: Horm Behav. 1993 Dec;27(4):568-83
references.pmid: 8294123
references.citation: Psychopharmacology (Berl). 2007 Mar;191(1):119-25
references.pmid: 17096081
references.citation: J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):261-6
references.pmid: 17113983
references.citation: Best Pract Res Clin Endocrinol Metab. 2008 Apr;22(2):389-402
references.pmid: 18471794
references.citation: Behav Neurosci. 1994 Apr;108(2):325-32
references.pmid: 8037876
references.citation: Fertil Steril. 2008 Jul;90(1):165-73
references.pmid: 18001721
references.citation: Psychoneuroendocrinology. 1991;16(4):323-34
references.pmid: 1745699
references.citation: Neurotoxicol Teratol. 2009 Jan-Feb;31(1):1-10
references.pmid: 18930132
references.citation: Neuropsychopharmacology. 2005 Sep;30(9):1598-609
references.pmid: 15798780
references.citation: Psychoneuroendocrinology. 2003 Oct;28(7):863-74
references.pmid: 12892654
references.citation: Aging Male. 2002 Mar;5(1):47-51
references.pmid: 12040975
references.citation: Mol Neurobiol. 1988 Winter;2(4):291-317
references.pmid: 2855977
references.citation: Behav Brain Res. 2001 Aug 27;123(1):65-76
references.pmid: 11377730
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Sep;14(9):2257-60
references.pmid: 16172240
references.citation: Biol Reprod. 1987 Oct;37(3):628-33
references.pmid: 3676409
references.citation: Pharmacol Biochem Behav. 2004 Jul;78(3):559-68
references.pmid: 15251265
references.citation: Pharmacol Biochem Behav. 1999 Dec;64(4):777-85
references.pmid: 10593201
references.citation: Curr Med Chem. 2007;14(25):2680-701
references.pmid: 17979718
references.citation: Neuropsychopharmacology. 2008 Apr;33(5):1049-61
references.pmid: 17625503