Chronic corticosterone impaired effortful motivation and risky decision-making in mice

Elevated risky decision-making is an established feature of major depressive disorder (MDD), but is not addressed by frontline treatments. The development of cross-species models of MDD focused on risky decision-making would enable high-throughput studies of novel therapeutics targeting these deficits. Elevated cortisol is observed in people with MDD and administering cortisol to healthy patients increases risky decision-making. Thus, the goal of this study was to determine whether increasing cortisol in experimental rodents also increases risky decision-making. Here, C57BL/6 J mice (n = 30, 50 % female) were given corticosterone (the rodent equivalent of cortisol) dissolved in drinking water (35 μg/mL for 21 days). Following chronic corticosterone administration, risky decision-making (Iowa gambling task; IGT), effortful motivation (progressive ratio breakpoint task; PRBT), reinforcement learning (probabilistic reversal learning task; PRLT) and exploratory behavior (Behavioral Pattern Monitor; BPM) were assessed. Chronic corticosterone elevated risky decision making (decreased difference score) and increased inappropriate responding during punishment phases in the IGT, suggesting that the sensitivity to negative outcomes contributed to impairments in decision-making. We also observed a decrease in breakpoint in the PRBT, indicating reduced effortful motivation, and a trend-level improvement in decision-making in the PRLT. Chronic corticosterone did not affect activity or exploration (BPM). Together, these findings mirror those of clinical studies of depression, supporting the use of chronic corticosterone as a model of risk-taking in MDD. Thus, the connections between corticosterone and risky decision-making in the context of MDD can be further elucidated.