Activation of orexin neurons changes reward-based decision-making strategies

Orexin neurons regulate physiological functions, including not only energy homeostasis and wakefulness but also motivated behaviors. These neurons play important roles in linking metabolic requirements to such behaviors. However, it is unknown whether these neurons are involved in reward-based choice behavior. We recently developed a transgenic rat line that expresses Cre recombinase exclusively in orexin neurons. Here, we examined the roles of orexin neurons in reward choice behavior under conditions of uncertainty in a gambling test in rats and analyzed the changes in choice behavior when orexin neurons were manipulated using chemogenetic approaches. In the gambling test, chemogenetic activation of orexin neurons resulted in risky arm choice. Positive, but not negative, reward-prediction error contributed to reward-based risky choice when orexin neurons were activated. These risky choice behaviors were canceled by suvorexant, an orexin receptor antagonist. In addition, suvorexant administered alone led to conservative choice behavior. The computational approach revealed that orexin/orexin neurons modulate the learning process and motivational value of rewards. Thus, our data suggest that orexin/orexin neurons affect the processing of reward-prediction error and alter strategy in reward-based decision-making.