Background
Ovarian hormones may contribute to the vulnerability to depression, as well as to
the response to antidepressants (ADs). Previously, we reported that acute systemic
treatment with estradiol or progesterone blocked the ability of the selective serotonin
reuptake inhibitor, fluvoxamine, to inhibit serotonin transporter function in ovariectomized
rats. In this study, behavioral consequences, as well as receptor mechanisms underlying
these hormonal effects, were investigated.
Methods
Using the forced swimming test, the acute effect of estradiol and/or progesterone
on fluvoxamine's AD-like effects was investigated. Using in vivo chronoamperometry,
the effect of local application of estradiol or progesterone into the hippocampus
of ovariectomized rats on serotonin (5-HT) clearance, as well as on the ability of
fluvoxamine to slow 5-HT clearance, were investigated.
Results
The decreased immobility and increased swimming caused by fluvoxamine in the forced
swimming test was blocked in rats treated with estradiol and/or progesterone. Local
application of estradiol, but not progesterone, slowed 5-HT clearance and both hormones
blocked the ability of fluvoxamine to slow 5-HT clearance. Use of hormone receptor
agonists and antagonists, revealed that the effects of estradiol are mediated by activation
of membrane, as well as nuclear estrogen receptors (ER). The AD-like effect of estradiol
involved ER beta and G-protein coupled receptor 30, whereas its blockade of fluvoxamine's
effects was ER alpha-mediated. The effects of progesterone occurred solely by activation
of intracellular progesterone receptors.
Conclusions
Targeting of ER beta or G-protein coupled receptor 30 might reveal a strategy to permit
beneficial effects of estrogen without its deleterious effect on selective serotonin
reuptake inhibitor efficacy.
Key Words
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Article info
Publication history
Published online: January 09, 2012
Accepted:
November 30,
2011
Received in revised form:
November 29,
2011
Received:
February 8,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
