Major advances in the past decade have led a better understanding of the pathophysiology of
narcolepsy with
cataplexy (NC) caused by the early loss of hypothalamic
hypocretin neurons. Although a role for
hypocretin in the regulation of sleep/wakefulness state is widely recognized, other functions, not necessarily related to arousal, have been identified. Hence, the
hypocretin system enhances signaling in the mesolimbic pathways regulating reward processing, emotion and mood regulation, and addiction. Although studies on
hypocretin-deficient mice have shown that
hypocretin plays an essential role in reward-seeking, depression-like behavior and addiction, results in human
narcolepsy remained subject to debate. Most of studies revealed that
hypocretin-deficient
narcolepsy patients either
drug-free or medicated with psychostimulant had preferences toward risky choices in a decision-making task under ambiguity together with higher frequency of depressive symptoms and
binge eating disorder compared to controls. However, human studies mostly reported the lack of association with pathological impulsivity and
gambling, and substance and
alcohol abuse in the context of
narcolepsy-
cataplexy. Prospective larger studies are required to confirm these findings in
drug-free and medicated patients with
narcolepsy. Inclusion of patients with other central
hypersomnias without
hypocretin deficiency will provide answer to the major question of the role of the
hypocretin system in reward-based behaviors and emotional processing in humans.