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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.

When pre-surgery stable behavior was compared between males (n = 27) and females (n = 31), significant sex differences emerged whereby males chose the large, risky reward significantly more than females. Data are represented as the mean ± SEM percent choice of the large, risky reward. An asterisk indicates statistical significance.

a Prior to surgery, there were no differences in choice of the large, risky reward between female rats that would go on to receive sham (n = 15) or ovariectomy (OVX; n = 16) surgeries. b After surgery, there was a significant increase in choice of the large, risky reward in OVX females relative to sham females. c Prior to surgery, there were no differences in win-stay or lose-shift performance between rats that would go on to receive sham or OVX surgeries. d After surgery, there were no differences in win-stay or lose-shift performance between sham and OVX rats. e There were no differences in the number of lever presses between OVX and sham females on a progressive ratio (PR) schedule of reinforcement. f There were no differences in shock sensitivity between OVX and sham females. Data are represented as the mean ± SEM percent choice of the large, risky reward (a, b), proportion of trials (c, d), number of lever presses (e) or shock sensitivity thresholds (f). An asterisk indicates statistical significance.

a Prior to surgery, there were no differences in choice of the large, risky reward between male rats that would go on to receive sham (n = 14) or orchiectomy (ORX; n = 13) surgeries. b After surgery, there was a significant decrease in choice of the large, risky reward in ORX males relative to sham males. c Prior to surgery, there were no differences in win-stay or lose-shift performance between rats that would go on to receive sham or ORX surgeries. d After surgery, there was a significant reduction in win-stay behavior in ORX rats compared to sham rats. e There were no differences in the number of lever presses between ORX and sham males on a PR schedule of reinforcement. f There were no differences in shock sensitivity between ORX and sham males. Data are represented as the mean ± SEM percent choice of the large, risky reward (a, b), proportion of trials (c, d), number of lever presses (e), or shock sensitivity thresholds (f). An asterisk indicates statistical significance.

a There were no effects of estradiol benzoate (EB) administration on choice of the large, risky reward in sham females (n = 15). b EB administration decreased choice of the large, risky reward in ovariectomized (OVX) females (n = 16). c There were no effects of EB administration on win-stay or lose-shift performance in sham females. d EB administration reduced win-stay behavior in OVX females, but had no effect on lose-shift behavior. EB administration reduced lever pressing for food in sham (e) but not OVX (f) females. g There were no effects of EB in either OVX or sham female rats. Data are represented as the mean ± SEM percent choice of the large, risky reward (a, b), proportion of trials (c, d), number of lever presses (e, f), or shock sensitivity thresholds (g). An asterisk indicates statistical significance.

a There were no effects of testosterone (T) on choice of the large, risky reward in sham males (n = 14). b There were no effects of T on choice of the large, risky reward in orchiectomized (ORX) males (n = 13). c Estradiol benzoate (EB) administration caused a significant reduction in lever presses to obtain the large, risky reward in sham males (n = 7). d EB administration caused a significant decrease in lever presses for the large, risky reward in ORX males (n = 7). e EB administration reduced win-stay behavior in sham males, but had no effect on lose-shift behavior. f EB administration reduced win-stay behavior in ORX males, but had no effect on lose-shift behavior. g, h There was no effect of EB administration on lever pressing in either sham (g; n = 7) or ORX (h; n = 7) males. Data are represented as the mean ± SEM percent choice of the large, risky reward (a–d), proportion of trials (e, f), number of lever presses (g, h), or shock sensitivity thresholds (g). An asterisk indicates statistical significance.

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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. (2020). https://doi.org/10.1038/s41386-020-00827-0

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