We have summarized some of the primary behavioral and physiological processes in which orexins participate and note that orexins' roles are conditional for each process. Orexin neurons are involved in arousal, sleep/wake, homeostatic and metabolic regulation, but these functions vary according to motivational state, sleep pressure, circadian rhythms and other variables. Orexins facilitate reward seeking, but only when this seeking is highly motivated by a physiological need, such as hunger, and/or by a psychological need triggered by substantial external stimuli, such as cues or stressors. Orexins help coordinate stress responses, but only for certain acute stressors in which escape or other coping strategies occur, and not when stress is chronic, predictable and inescapable. Orexins can also facilitate attention, but are only involved in certain types of emotional learning.
We propose that a common theme underlying these diverse processes is recruitment of the orexin system during motivational activation triggered by internal (homeostatic) or external (motivationally relevant) signals of threat or opportunity. We also propose that orexins fundamentally function to facilitate adaptive, often highly motivated behavior by coordinating psychological and physiological responses supporting such behaviors to address the threat or opportunity at hand. However, if orexins function in this integrated manner, heterogeneity at some level must modulate the orexin system to allow coordination of diverse, contextually appropriate behaviors, adding flexibility and variety to orexins' unified function.
