Abstract

Fear extinction is the laboratory basis of exposure therapy for anxiety disorders. Recent findings have revealed that estradiol is necessary to the consolidation of extinction memories in females. These findings are based on studies conducted using virgin rats and young women whose reproductive history is unknown. We hypothesized that motherhood, which results in extensive endocrinological, neurobiological and behavioral changes, may lead to alterations in fear extinction in females. We used a cross-species translational approach to investigate the impact of reproductive experience on fear extinction and fear relapse in female rats (n=116) and women (n=64). Although freezing during extinction recall was associated with estrous cycle phase during extinction training in virgin rats, this association was mitigated in age-matched reproductively experienced rats, even when fear extinction occurred 3 months after pups had been weaned, and even though reproductively experienced rats exhibited attenuated serum estradiol levels. In addition, although serum estradiol levels predicted extinction recall in human women with no prior reproductive experience, no such association was found in women with children. Finally, although virgin rats displayed both renewal and reinstatement after fear extinction, these common relapse phenomena were absent in rats with reproductive experience. Together, these findings suggest that reproductive experience alters the endocrine and behavioral features of fear extinction in females long after the hormonal surges of pregnancy and lactation have diminished. These results highlight the need to incorporate both hormonal and reproductive status as important factors in current models of fear extinction in females.

Highlights

  • Anxiety disorders are characterized by deficits in fear inhibition, which can be studied in rats and humans using fear extinction.[1]

  • Serum estradiol levels predicted extinction recall in human women with no prior reproductive experience, no such association was found in women with children

  • These findings suggest that reproductive experience alters the endocrine and behavioral features of fear extinction in females long after the hormonal surges of pregnancy and lactation have diminished

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Summary

ORIGINAL ARTICLE

Mothers do it differently: reproductive experience alters fear extinction in female rats and women. Recent findings have revealed that estradiol is necessary to the consolidation of extinction memories in females These findings are based on studies conducted using virgin rats and young women whose reproductive history is unknown. Virgin rats displayed both renewal and reinstatement after fear extinction, these common relapse phenomena were absent in rats with reproductive experience. Together, these findings suggest that reproductive experience alters the endocrine and behavioral features of fear extinction in females long after the hormonal surges of pregnancy and lactation have diminished. Translational Psychiatry (2016) 6, e928; doi:10.1038/tp.2016.193; published online 25 October 2016

INTRODUCTION
MATERIALS AND METHODS
RESULTS
Another question of interest is whether the effects of ACKNOWLEDGMENTS
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