418. ROLE OF OREXIN IN REWARD-BASED DECISION-MAKING STRATEGIES

Abstract Background Orexin neurons regulate physiological functions, including not only energy homeostasis and wakefulness, but also motivated behaviors. However, it is unknown whether these neurons are involved in reward choice strategy. We recently developed a transgenic rat line that expresses Cre recombinase exclusively in orexin neurons. Aims & Objectives 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. Method We developed a transgenic rat line that expresses Cre recombinase exclusively in orexin neurons. We used rat gambling test using a radial arm maze to examine decision-making strategies. Results In the gambling test, cell-specific excitatory manipulation of orexin neurons using chemogenetics 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 behaviors were inhibited by suvorexant, orexin receptor antagonist, treatment. Suvorexant alone also induced conservative choice behaviors. Discussion & Conclusions Our data suggest that activated orexin neurons affect the processing of reward prediction error and alter strategy in reward-based decision-making.