Background
Men and women differ in their ability to extinguish fear. Fear extinction requires
the activation of brain regions, including the ventromedial prefrontal cortex (vmPFC)
and amygdala. Could estradiol modulate the activity of these brain regions during
fear extinction?
Methods
All rat experiments were conducted in naturally cycling females. Rats underwent fear
conditioning on Day 1. On Day 2, they underwent extinction training during the metestrus
phase of the cycle (low estrogen and progesterone). Extinction recall was assessed
on Day 3. Systemic injections of estrogen receptor-beta and -alpha agonists and of
estradiol were administered at different time points to assess their influence on
extinction consolidation and c-Fos expression in the vmPFC and amygdala. In parallel,
healthy naturally cycling women underwent an analogous fear conditioning extinction
training in a 3T functional magnetic resonance scanner. Measurement of their estradiol
levels and skin conductance responses were obtained throughout the experiment.
Results
In female rats, administration of the estrogen-receptor beta (but not alpha) agonist
facilitated extinction recall. Immediate (but not delayed) postextinction training
administration of estradiol facilitated extinction memory consolidation and increased
c-Fos expression in the vmPFC while reducing it in the amygdala. In parallel, natural
variance in estradiol in premenopausal cycling women modulated vmPFC and amygdala
reactivity and facilitated extinction recall.
Conclusions
We provide translational evidence that demonstrates the influence of endogenous and
exogenous estradiol on the fear extinction network. Our data suggest that women's
endogenous hormonal status should be considered in future neurobiological research
related to anxiety and mood disorders.
Key Words
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Article info
Publication history
Published online: July 18, 2011
Accepted:
May 9,
2011
Received in revised form:
April 25,
2011
Received:
March 15,
2011
Identification
Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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- Complex Roles of Estrogen in Emotion: Sex MattersBiological PsychiatryVol. 70Issue 10
- PreviewWomen are more than twice as likely to suffer from fear and anxiety disorders, including generalized anxiety disorder, panic attacks, and posttraumatic stress disorder. One reason for this difference may be that fluctuating ovarian hormone levels in women during their reproductive life span alters emotional processing. For example, the incidence of anxiety symptoms is higher when ovarian hormone levels are low, including during premenstrual, postpartum, and perimenopausal periods. These women can benefit from estrogen treatment, suggesting an anxiolytic effect.
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