Opiate anticipation, opiate induced anatomical changes in hypocretin (Hcrt, orexin) neurons and opiate induced microglial activation are blocked by the dual Hcrt receptor antagonist suvorexant, while opiate analgesia is maintained.

We previously found that heroin addiction in humans is accompanied by an increase in the number of detected Hcrt neurons and a decrease in their soma size. We now show that the increased number of Hcrt cells visible after morphine treatment is likely the result of increased Hcrt production in neurons having sub-detection levels of the peptides. We find that morphine increases Hcrt projections to the ventral tegmental area (VTA), the level of tyrosine hydroxylase enzyme (TH) and the number of TH positive cells in VTA, with no changes in the adjacent substantia nigra.

Effects of sodium oxybate on hypocretin/orexin and locus coeruleus neurons.

Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found that chronic opiate usage in humans and long-term opiate administration to mice significantly increased the number of detected hypocretin/orexin (Hcrt) neurons, decreased their size, and increased Hcrt level in the hypothalamus. We also found that opiates significantly decreased cataplexy in human narcoleptics as well as in narcoleptic mice and that cessation of locus coeruleus neuronal activity preceded and was tightly linked to cataplectic attacks in narcoleptic dogs.

Sensitivity of Hypocretin System to Chronic Alcohol Exposure: A Human and Animal Study.

Human heroin addicts and mice administered morphine for a 2 week period show a greatly increased number of hypothalamic hypocretin (Hcrt or orexin) producing neurons with a concomitant reduction in Hcrt cell size. Male rats addicted to cocaine similarly show an increased number of detectable Hcrt neurons. These findings led us to hypothesize that humans with alcohol use disorder (AUD) would show similar changes.

Nuclear organization of orexinergic neurons in the hypothalamus of a lar gibbon and a chimpanzee.

Employing orexin-A immunohistochemical staining we describe the nuclear parcellation of orexinergic neurons in the hypothalami of a lar gibbon and a chimpanzee. The clustering of orexinergic neurons within the hypothalamus and the terminal networks follow the patterns generally observed in other mammals, including laboratory rodents, strepsirrhine primates and humans. The orexinergic neurons were found within three distinct clusters in the ape hypothalamus, which include the main cluster, zona incerta cluster and optic tract cluster.