Abstract
Orexin peptides comprise two neuropeptides, orexin A and orexin B, that bind two G-protein coupled receptors (GPCRs), orexin receptor 1 (OXR1) and orexin receptor 2 (OXR2). Although cell bodies that produce orexin peptides are localized in a small area comprising the lateral hypothalamus and adjacent regions, orexin-containing fibres project throughout the neuraxis. Although orexins were initially described as peptides that regulate feeding behaviour, research has shown that orexins are involved in diverse functions that range from the modulation of autonomic functions to higher cognitive functions, including reward-seeking, behaviour, attention, cognition, and mood. Furthermore, disruption in orexin signalling has been shown in mood disorders that are associated with low hedonic tone or anhedonia, including depression, anxiety, attention deficit hyperactivity disorder, and addiction. Notably, projections of orexin neurons overlap circuits involved in the modulation of hedonic tone. Evidence shows that orexins may potentiate hedonic behaviours by increasing the feeling of pleasure or reward to various signalling, whereas dysregulation of orexin signalling may underlie low hedonic tone or anhedonia. Further, orexin appears to play a key role in regulating behaviours in motivationally charged situations, such as food-seeking during hunger, or drug-seeking during withdrawal. Therefore, it would be expected that dysregulation of orexin expression or signalling is associated with changes in hedonic tone. Further studies investigating this association are warranted.
Highlights
Publisher’s Note: MDPI stays neutralNeuropeptides orexin A and orexin B were first described in the late 1990s and were initially shown to regulate feeding behaviour [1,2]
It has been shown that orexins are involved in diverse functions that range from the modulation of autonomic functions, and promotion of physical activity, as well as reward-seeking behaviour and higher cognitive functions, including attention, cognition, and mood [3,4]
Neuroanatomical studies have further supported the role of the orexin system in sleep and wakefulness by demonstrating that orexin-containing neurons project to key brain regions involved in the regulation of sleep-wake cycles, including histaminergic neurons in the tuberomammillary nucleus (TMN), cholinergic and GABAergic neurons of the basal forebrain, dopaminergic neurons within the ventral tegmental area (VTA), and norepinephrine neurons in the locus coeruleus (LC) [17]
Summary
Neuropeptides orexin A and orexin B were first described in the late 1990s and were initially shown to regulate feeding behaviour [1,2]. Since their discovery, it has been shown that orexins are involved in diverse functions that range from the modulation of autonomic functions (i.e., food intake, sleep regulation, and cardiovascular function), and promotion of physical activity, as well as reward-seeking behaviour and higher cognitive functions, including attention, cognition, and mood [3,4].
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