Abstract
Background
Estrogen increases dramatically during pregnancy but quickly drops below prepregnancy
levels at birth and remains suppressed during the postpartum period. Clinical and
rodent work suggests that this postpartum drop in estrogen results in an estrogen
withdrawal state that is related to changes in affect, mood, and behavior. How estrogen
withdrawal affects oxytocin (OT) neurocircuitry has not been examined.
Methods
We used a hormone-simulated pseudopregnancy followed by estrogen withdrawal in Syrian
hamsters, a first for this species. Ovariectomized females were given daily injections
to approximate hormone levels during gestation and then withdrawn from estrogen to
simulate postpartum estrogen withdrawal. These hamsters were tested for behavioral
assays of anxiety and anhedonia during estrogen withdrawal. Neuroplasticity in OT-producing
neurons in the paraventricular nucleus of the hypothalamus and its efferent targets
was measured.
Results
Estrogen-withdrawn females had increased anxiety-like behaviors in the elevated plus
maze and open field tests but did not differ from control females in sucrose preference.
Furthermore, estrogen-withdrawn females had more OT-immunoreactive cells and OT messenger
RNA in the paraventricular nucleus of the hypothalamus and an increase in OT receptor
density in the dorsal raphe nucleus. Finally, blocking OT receptors in the dorsal
raphe nucleus during estrogen withdrawal prevented the high-anxiety behavioral phenotype
in estrogen-withdrawn females.
Conclusions
Estrogen withdrawal induces OT neuroplasticity in the paraventricular nucleus of the
hypothalamus and dorsal raphe nucleus to increase anxiety-like behavior during the
postpartum period. More broadly, these experiments suggest Syrian hamsters as a novel
organism in which to model the effects of postpartum estrogen withdrawal on the brain
and anxiety-like behavior.
Keywords
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Article Info
Publication History
Published online: November 23, 2020
Accepted:
November 11,
2020
Received in revised form:
November 11,
2020
Received:
June 16,
2020
Identification
Copyright
© 2020 Society of Biological Psychiatry.
