Orexin (hypocretin) is a neuropeptide that originates from the dorsal tuberal hypothalamus in an area that corresponds to the classic hypothalamic defense area. In terms of research, orexin neurons are to the hypothalamic defense area what the C1 group has been to the rostral ventrolateral medulla: a unique group of neurons, easy to identify and characterize, that will help to understand the functions and connections of the hypothalamic defense area.
Orexin neurons and orexin itself are implicated in the control of all aspects of arousal, including its cardiorespiratory component. Furthermore, orexin neurons target all the known central autonomic centers from limbic forebrain to the intermediolateral column.
Recent pharmacological studies with the dual orexin receptor antagonist Almorexant in the anaesthetized rat show that orexin contributes to half or more of the cardiorespiratory response to disinhibition of the hypothalamic defense area (~50% for the cardiac and pressor response, ~70% for the respiratory response). Similar studies in the behaving animal also show an important contribution to the behavioral and cardiovascular response of some forms of stress such as social stress, conditioned fear and novelty (~45% of the cardiac and pressor responses), but not restraint. Further work is in progress to understand the role of the two orexin receptors and to identify the relays, in the lower brainstem or at spinal level, at which orexin exerts these effects.
Orexin neurons offer a unique opportunity to explore and understand the function of the classic hypothalamic defense area. Drugs blocking orexin receptors may also become useful tools in the management of stress-induced sympathetic responses.