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Regulation of risky decision making by gonadal hormones in males and females

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Abstract

Psychiatric diseases characterized by dysregulated risky decision making are differentially represented in males and females. The factors that govern such sex differences, however, remain poorly understood. Using a task in which rats make discrete trial choices between a small, “safe” food reward and a large food reward accompanied by varying probabilities of footshock punishment, we recently showed that females are more risk averse than males. The objective of the current experiments was to test the extent to which these sex differences in risky decision making are mediated by gonadal hormones. Male and female rats were trained in the risky decision-making task, followed by ovariectomy (OVX), orchiectomy (ORX), or sham surgery. Rats were then retested in the task, under both baseline conditions and following administration of estradiol and/or testosterone. OVX increased choice of the large, risky reward (increased risky choice), an effect that was attenuated by estradiol administration. In contrast, ORX decreased risky choice, but testosterone administration was without effect in either ORX or sham males. Estradiol, however, decreased risky choice in both groups of males. Importantly, none of the effects of hormonal manipulation on risky choice were due to altered shock sensitivity or food motivation. These data show that gonadal hormones are required for maintaining sex-typical profiles of risk-taking behavior in both males and females, and that estradiol is sufficient to promote risk aversion in both sexes. The findings provide novel information about the mechanisms supporting sex differences in risk taking and may prove useful in understanding sex differences in the prevalence of psychiatric diseases associated with altered risk taking.

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Fig. 1: Sex differences in risky decision making.
Fig. 2: Effects of ovariectomies on risky decision making in females.
Fig. 3: Effects of orchiectomies on risky decision making in males.
Fig. 4: Effects of estradiol benzoate administration on risky decision making in sham and ovariectomized females.
Fig. 5: Effects of testosterone and estradiol on risky decision making in sham and orchiectomized males.

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Acknowledgements

We thank Ms. Bonnie McLaurin for her role in gonadectomy surgeries. We are additionally grateful to Mr Matt Bruner, Ms Shannon Wall, and Ms Vicky Kelley for their assistance with behavioral testing.

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CAO and BS designed the experiments. CAO, SLB, CMH, SMB, HP, ARW, TWT, TSG conducted experiments. CAO, SMB, CMH, and TSG performed data analyses. CAO, BS, and JLB wrote the manuscript.

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Correspondence to Barry Setlow.

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Orsini, C.A., Blaes, S.L., Hernandez, C.M. et al. Regulation of risky decision making by gonadal hormones in males and females. Neuropsychopharmacol. 46, 603–613 (2021). https://doi.org/10.1038/s41386-020-00827-0

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