Hypocretin/Orexin Interactions with Norepinephrine Contribute to the Opiate Withdrawal Syndrome.

Autor:	McGregor R; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095 icelos3@gmail.com.; Veterans Administration Greater Los Angeles Healthcare System, North Hills, Los Angeles, California 91343., Wu MF; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095.; Veterans Administration Greater Los Angeles Healthcare System, North Hills, Los Angeles, California 91343., Holmes B; Veterans Administration Greater Los Angeles Healthcare System, North Hills, Los Angeles, California 91343.; Department of Medicine, University of California, Los Angeles, Los Angeles, 90095., Lam HA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095.; Hatos Center for Neuropharmacology, University of California, Los Angeles, Los Angeles, California 90095., Maidment NT; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095.; Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90095.; Hatos Center for Neuropharmacology, University of California, Los Angeles, Los Angeles, California 90095., Gera J; Veterans Administration Greater Los Angeles Healthcare System, North Hills, Los Angeles, California 91343.; Department of Medicine, University of California, Los Angeles, Los Angeles, 90095.; Jonnson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, 90095.; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, 90095., Yamanaka A; Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan., Siegel JM; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095.; Veterans Administration Greater Los Angeles Healthcare System, North Hills, Los Angeles, California 91343.; Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90095.
Jazyk:	angličtina
Zdroj:	The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2022 Jan 12; Vol. 42 (2), pp. 255-263. Date of Electronic Publication: 2021 Dec 01.
DOI:	10.1523/JNEUROSCI.1557-21.2021
Abstrakt:	We previously found that human heroin addicts and mice chronically exposed to morphine exhibit a significant increase in the number of detected hypocretin/orexin (Hcrt)-producing neurons. However, it remains unknown how this increase affects target areas of the hypocretin system involved in opioid withdrawal, including norepinephrine containing structures locus coeruleus (LC) and A1/A2 medullary regions. Using a combination of immunohistochemical, biochemical, imaging, and behavioral techniques, we now show that the increase in detected hypocretin cell number translates into a significant increase in hypocretin innervation and tyrosine hydroxylase (TH) levels in the LC without affecting norepinephrine-containing neuronal cell number. We show that the increase in TH is completely dependent on Hcrt innervation. The A1/A2 regions were unaffected by morphine treatment. Manipulation of the Hcrt system may affect opioid addiction and withdrawal. SIGNIFICANCE STATEMENT Previously, we have shown that the hypothalamic hypocretin system undergoes profound anatomic changes in human heroin addicts and in mice exposed to morphine, suggesting a role of this system in the development of addictive behaviors. The locus coeruleus plays a key role in opioid addiction. Here we report that the hypothalamic hypocretin innervation of the locus coeruleus increases dramatically with morphine administration to mice. This increase is correlated with a massive increase in tyrosine hydroxylase expression in locus coeruleus. Elimination of hypocretin neurons prevents the tyrosine hydroxylase increase in locus coeruleus and dampens the somatic and affective components of opioid withdrawal. (Copyright © 2022 the authors.)
Databáze:	MEDLINE
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