Linked Life Data

18775724

Source:http://linkedlifedata.com/resource/pubmed/id/18775724

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-10-30
pubmed:abstractText
Testosterone (T) and its metabolites may underlie some beneficial effects for anxiety and cognition, but the mechanisms for these effects are unclear. T is reduced to dihydrotestosterone (DHT), which can be converted to 5alpha-androstane,3alpha,17beta-diol (3alpha-diol) and/or 5alpha-androstane-3beta,17beta-diol (3beta-diol). Additionally, T can be converted to androstenedione, and then to androsterone. These metabolites bind with varying affinity to androgen receptors (ARs; T and DHT), estrogen receptors (ERbeta; 3alpha-diol, 3beta-diol), or GABA(A)/benzodiazepine receptors (GBRs; 3alpha-diol, androsterone). Three experiments were performed to investigate the hypothesis that reduced anxiety-like and enhanced cognitive performance may be due in part to actions of T metabolites at ERbeta. Experiment 1: Gonadectomized (GDX) wildtype and ERbeta knockout mice (betaERKO) were subcutaneously (SC) administered 3alpha-diol, 3beta-diol, androsterone, or oil vehicle at weekly intervals, and tested in anxiety tasks (open field, elevated plus maze, light-dark transition) or for cognitive performance in the object recognition task. Experiment 2: GDX rats were administered SC 3alpha-diol, 3beta-diol, androsterone, or oil vehicle, and tested in the same tasks. Experiment 3: GDX rats were androsterone- or vehicle-primed and administered an antagonist of ARs (flutamide), ERs (tamoxifen), or GBRs (flumazenil), or vehicle and then tested in the elevated plus maze. Both rats and wildtype mice, but not betaERKO mice, consistently had reduced anxiety and improved performance in the object recognition task. Androsterone was only effective at reducing anxiety-like behavior in the elevated plus maze and this effect was modestly reduced by flumazenil administration. Thus, actions at ERbeta may be required for T's anxiety-reducing and cognitive-enhancing effects.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1095-6867
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
726-34
pubmed:meshHeading
pubmed-meshheading:18775724-Adaptation, Ocular, pubmed-meshheading:18775724-Adaptation, Psychological, pubmed-meshheading:18775724-Androgen Antagonists, pubmed-meshheading:18775724-Androgens, pubmed-meshheading:18775724-Androsterone, pubmed-meshheading:18775724-Animals, pubmed-meshheading:18775724-Anti-Anxiety Agents, pubmed-meshheading:18775724-Anxiety, pubmed-meshheading:18775724-Brain, pubmed-meshheading:18775724-Cognition, pubmed-meshheading:18775724-Estrogen Receptor beta, pubmed-meshheading:18775724-Male, pubmed-meshheading:18775724-Maze Learning, pubmed-meshheading:18775724-Mice, pubmed-meshheading:18775724-Mice, Inbred C57BL, pubmed-meshheading:18775724-Mice, Knockout, pubmed-meshheading:18775724-Nootropic Agents, pubmed-meshheading:18775724-Pattern Recognition, Visual, pubmed-meshheading:18775724-Rats, pubmed-meshheading:18775724-Rats, Long-Evans
pubmed:year
2008
pubmed:articleTitle
Androgens with activity at estrogen receptor beta have anxiolytic and cognitive-enhancing effects in male rats and mice.
pubmed:affiliation
Department of Psychology, The University at Albany-SUNY, NY 12222, USA. cafrye@albany.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Evaluation Studies, Research Support, N.I.H., Extramural