Sex Differences in Risk-based Decision Making

Decision-making is a complex process essential to daily adaptation in many species. Risk is an inherent aspect of decision-making and it is influenced by gonadal hormones. Testosterone and 17β-estradiol may modulate decision making and impact the mesocorticolimbic dopamine pathway. Here, we explored sex differences, the effect of gonadal hormones and the dopamine agonist amphetamine on risk-based decision making. Intact or gonadectomised (GDX) male and female rats underwent to a probabilistic discounting task. High and low doses of testosterone propionate (1.0 or 0.2 mg) and 17β-estradiol benzoate (0.3 µg) were administered to assess acute effects on risk-based decision making. After 3-days of washout period, intact and GDX rats received high or low (0.5 or 0.125 mg/kg) doses of amphetamine and re-tested in the probabilistic discounting task. Results showed that males made more risk-based choices during the probability discounting task than female rats, but GDX did not influence risky choices. The high dose, but not the low dose, of testosterone reduced risky decision making in GDX male rats. However, 17β-estradiol had no significant effect on risk-based decision making regardless GDX status in either sex. Lastly, the high dose of amphetamine enhanced risky decision making in both intact males and females, with no effect in GDX rats. These findings demonstrated sex differences in risk-based decision making, with males making more risky choices. GDX status influenced the effects of amphetamine, suggesting different dopaminergic regulation in risk-based choices among males and females. Highlights Male rats made more risky choices in the probability discounting task than females. Gonadectomy (GDX) did not influence risk-based decision making in both sexes. A high dose of testosterone reduced risky choices in GDX male rats. A high dose of amphetamine enhanced risky choices in intact male and female rats. 17β-estradiol did not affect risk-based decision making in male or female rats.