Fig. 1.
Orexin receptor distribution and potential application of orexin receptor antagonists for the treatment of psychiatric disorders. A Orexin neurons in the lateral hypothalamus send extensive projections to brain areas associated with feeding, sleep-wake regulation, and motivated and emotional behaviors. The anatomical distribution of OX1Rs and OX2Rs in these regions is shown. B Orexin A and orexin B are hypothalamic neuropeptides. Their actions are mediated by Gq- and/or Gi/o-coupled OX1Rs and OX2Rs, playing important roles in many physiological processes, such as feeding, the sleep-to-wakefulness transition, and motivation. Antagonism of the orexin system increases NREM and REM sleep, decreases anxiety- and panic-like behaviors, and inhibits the reinforcing and motivational properties of addictive drugs. Orexin receptor antagonists may be promising for the treatment of psychiatric disorders, such as insomnia, anxiety, and drug addiction. BNST, bed nucleus of the stria terminalis; CeA, central nucleus of the amygdala; DORA, dual OX1/2R antagonist; DR, dorsal raphe; Hip, hippocampus; LC, locus coeruleus; LDT/PPT, laterodorsal tegmental nucleus/pedunculopontine nucleus; LH, lateral hypothalamus; mPFC, medial prefrontal cortex; NAc, nucleus accumbens; NREM, non-rapid-eye-movement; NTS, nucleus of the solitary tract; OX1R, orexin type 1 receptor; OX2R, orexin type 2 receptor; PVN, hypothalamic paraventricular nucleus; REM, rapid-eye-movement; SORA1, selective OX1R antagonist; SORA2, selective OX2R antagonist; TMN, tuberomammillary nucleus; VTA, ventral tegmental area.