PMID- 17625503
OWN - NLM
STAT- MEDLINE
DCOM- 20080801
LR  - 20191210
IS  - 0893-133X (Print)
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Linking)
VI  - 33
IP  - 5
DP  - 2008 Apr
TI  - Androgen administration to aged male mice increases anti-anxiety behavior and 
      enhances cognitive performance.
PG  - 1049-61
AB  - Although androgen secretion is reduced with aging, and may underlie decrements in 
      cognitive and affective performance, the effects and mechanisms of androgens to 
      mediate these behaviors are not well understood. Testosterone (T), the primary 
      male androgen, is aromatized to estrogen (E(2)), and reduced to 
      dihydrotestosterone (DHT), which is converted to 5alpha-androstane, 3alpha, 
      17beta-diol (3alpha-diol). To ascertain whether actions of the neuroactive 
      metabolite of T, 3alpha-diol, mediates cognitive and affective behaviors, intact, 
      aged male C57/B6 mice (24 month old) as well as young, intact and gonadectomized 
      (GDX; 12 week old) mice were administered s.c. T, 3alpha-diol, E(2), or sesame 
      oil vehicle (1 mg/kg; n=4-5/group) at weekly intervals and 1 h later mice were 
      tested in the activity box, roto-rod, open field, elevated plus maze, zero maze, 
      mirror maze, dark-light transition, forced swim, or Vogel tasks. Mice were 
      trained in the inhibitory avoidance or conditioned contextual fear and were 
      administered hormones following training and then were tested. After the last 
      test occasion, tissues were collected for evaluation of hormone levels and 
      effects on gamma-aminobutyric acid (GABA)-stimulated chloride flux. T, 
      3alpha-diol, or E(2) increased anti-anxiety and antidepressant behavior of aged, 
      intact mice in the open field, light-dark transition, mirror maze, and forced 
      swim tasks. T or 3alpha-diol, but not E(2), enhanced anti-anxiety behavior in the 
      elevated plus maze, zero maze, and the Vogel task, and increased motor behavior 
      in the activity monitor, latency to fall in the Roto-rod task, and cognitive 
      performance in the hippocampally-mediated, but not the amygdala-mediated, portion 
      of the conditioned fear task and in the inhibitory avoidance task. Anti-anxiety 
      and enhanced cognitive performance was associated with regimen that increased 
      plasma and hippocampal 3alpha-diol levels and GABA-stimulated chloride flux. 
      Similar patterns were seen among young, adult GDX but not in intact mice. Thus, 
      3alpha-diol can enhance affective and cognitive behavior of male mice.
FAU - Frye, Cheryl A
AU  - Frye CA
AD  - Department of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA. 
      cafrye@albany.edu
FAU - Edinger, Kassandra
AU  - Edinger K
FAU - Sumida, Kanako
AU  - Sumida K
LA  - eng
GR  - R01 MH067698/MH/NIMH NIH HHS/United States
GR  - R01 MH067698-05/MH/NIMH NIH HHS/United States
GR  - MH 06769801/MH/NIMH NIH HHS/United States
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070711
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Androgens)
RN  - 0 (Chlorides)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
SB  - IM
MH  - Age Factors
MH  - Aging/*drug effects/physiology
MH  - Analysis of Variance
MH  - Androgens/*administration & dosage/blood/classification
MH  - Animals
MH  - Anxiety/*drug therapy
MH  - Avoidance Learning/drug effects
MH  - Behavior, Animal/*drug effects
MH  - Chlorides/metabolism
MH  - Cognition/*drug effects
MH  - Conditioning, Psychological/drug effects
MH  - Exploratory Behavior/drug effects
MH  - Hippocampus/ultrastructure
MH  - Male
MH  - Maze Learning/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Orchiectomy/methods
MH  - Radioimmunoassay
MH  - Random Allocation
MH  - Synaptosomes/drug effects/metabolism
MH  - gamma-Aminobutyric Acid/pharmacology
PMC - PMC2572829
MID - NIHMS73897
COIS- DISCLOSURE/CONFLICT OF INTERESTS The authors neither have any conflict of 
      interest relating to the subject of this report nor do they have financial 
      holdings (stocks, bonds or donations of supplies or equipment) that a reasonable 
      person would construe as possibly influencing the objectivity of the report. 
      Professor Frye has received compensation as a consultant for The Biocontinuum 
      Group. She has received grant support from NSF, NIMH, NIDA, NIAA, The Department 
      of Defense and The Epilepsy Foundation of America.
EDAT- 2007/07/13 09:00
MHDA- 2008/08/02 09:00
PMCR- 2009/04/01
CRDT- 2007/07/13 09:00
PHST- 2007/07/13 09:00 [pubmed]
PHST- 2008/08/02 09:00 [medline]
PHST- 2007/07/13 09:00 [entrez]
PHST- 2009/04/01 00:00 [pmc-release]
AID - 1301498 [pii]
AID - 10.1038/sj.npp.1301498 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2008 Apr;33(5):1049-61. doi: 10.1038/sj.npp.1301498. 
      Epub 2007 Jul 11.