{triangleup}FOSB in the nucleus accumbens core is required for increased anxiety, but not decreased social motivation, following estrogen withdrawal in female mice

Clayton, W.; Courtney, M. Y.; Craig, L. E.; Moniz, H. E.; Gibbons, A. B.; Valentine, A. A.; Singh, A. K.; Gearinger, D. R.; Nestler, E. J.; Been, L. E.

doi:10.1101/2025.10.21.683778

bioRxiv · 10.1101/2025.10.21.683778

{triangleup}FOSB in the nucleus accumbens core is required for increased anxiety, but not decreased social motivation, following estrogen withdrawal in female mice

Clayton, W.·Courtney, M. Y.·Craig, L. E.·Moniz, H. E.·Gibbons, A. B.·Valentine, A. A.·Singh, A. K.·Gearinger, D. R.·Nestler, E. J.·Been, L. E.

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Abstract

During pregnancy, estrogen levels rise dramatically, but quickly drop to prepartum levels following birth, and remain suppressed until ovulation resumes. This "postpartum estrogen withdrawal" state has been linked to changes in the brain and behavior in humans and rodents. Previous research has demonstrated that following a hormone-simulated pseudopregnancy (HSP), an experimental model of postpartum estrogen withdrawal, female mice show increased anxiety-like behaviors and decreased social motivation. Further, these behavioral changes occur concurrently with an increase in {Delta}FOSB, a transcription factor associated with stable long-term plasticity, in the nucleus accumbens core. To test whether this increase in {Delta}FOSB is required for these behavioral changes, we used a viral-mediated gene transfer approach to prevent {Delta}FOSB-mediated transcription in the NAcC during HSP and found that it reduced the high-anxiety behavioral phenotype in estrogen-withdrawn females. However, preventing {Delta}FOSB-mediated transcription had little effect on social motivation. Together, these results suggest that postpartum estrogen withdrawal increases {Delta}FOSB in the NAc core to impact anxiety-like behaviors, but not social motivation, following estrogen withdrawal.

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Clayton, W., Courtney, M. Y., Craig, L. E., Moniz, H. E., Gibbons, A. B., Valentine, A. A., Singh, A. K., Gearinger, D. R., Nestler, E. J., Been, L. E.. 2025-10-22. {triangleup}FOSB in the nucleus accumbens core is required for increased anxiety, but not decreased social motivation, following estrogen withdrawal in female mice. https://doi.org/10.1101/2025.10.21.683778

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