Background
Human and animal studies suggest that testosterone may have antidepressant effects.
In this study, we sought to investigate the molecular mechanisms underlying the antidepressant
effects of testosterone within the hippocampus, an area that is fundamental in the
etiology of depression.
Methods
The effects of testosterone replacements in gonadectomized adult male rats were investigated
using the sucrose preference and forced swim tests. We explored possible effects of
testosterone on hippocampal neurogenesis and gene expression of stress-related molecules.
Through the use of viral vectors, we pursued the antidepressant molecular mechanism(s)
of testosterone in mediating anhedonia and manipulated extracellular signal-regulated
kinase 2 (ERK2) expression in the dentate gyrus in gonadectomized rats with testosterone
replacements.
Results
Testosterone had antidepressant effects, likely mediated by aromatization to estrogen
metabolites, in the sucrose preference and forced swim tests despite having no effects
on hippocampal cell proliferation or survival. We found a testosterone-dependent regulation
of hippocampal ERK2 expression. Functionally, reducing ERK2 activity within the dentate
gyrus induced anhedonia in gonadectomized rats receiving testosterone supplementation,
whereas the overexpression of ERK2 rescued this behavior in gonadectomized rats.
Conclusions
These results implicate a role for ERK2 signaling within the dentate gyrus area of
the hippocampus as a key mediator of the antidepressant effects of testosterone.
Key Words
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Article info
Publication history
Published online: January 24, 2012
Accepted:
November 30,
2011
Received in revised form:
November 7,
2011
Received:
August 23,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
