Opioidergic projections to sleep-active neurons in the ventrolateral preoptic nucleus

Opioidergic projections to sleep-active neurons in the ventrolateral preoptic nucleus Although opioids are known to influence sleep–wake regulation, the neuroanatomic substrate(s) mediating these effects remain unresolved. We hypothesized that the influence of opiates on sleep may be mediated, at least in part, by the ventrolateral preoptic nucleus (VLPO), a key cell group for producing behavioral sleep. By combining in situ hybridization for kappa and mu receptor mRNA with immunostaining of Fos expressed by VLPO cells during sleep we show that > 85% of sleep-active VLPO neurons contain mRNA for either or both opioid receptors. Microinfusions of a kappa receptor agonist into the VLPO region increased NREM sleep by 51% during the subjective night, whereas a mu receptor agonist increased wakefulness by 60% during the subjective day. The sleep- and wake-promoting effects of the kappa and mu agonists were blocked by prior administration of their respective antagonist. Combining retrograde tracing from the VLPO with immunohistochemistry for dynorphin (Dyn, the endogenous kappa receptor agonist) or endomorphin 1 (EM1, the endogenous mu receptor agonist) we show that the central lateral parabrachial subnucleus (PBcl) provides Dyn inputs to the VLPO, whereas hypothalamic histaminergic neurons provide EM1 inputs to the VLPO. In summary, results from the present study suggest that central opioid inputs to the VLPO may play a role in sleep–wake regulation and that the VLPO likely mediates the hypnotic response to high levels of opioid analgesics. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Opioidergic projections to sleep-active neurons in the ventrolateral preoptic nucleus

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Publisher
Elsevier
Copyright
Copyright © 2008 Elsevier B.V.
ISSN
0006-8993
DOI
10.1016/j.brainres.2008.09.043
Publisher site
See Article on Publisher Site

Abstract

Although opioids are known to influence sleep–wake regulation, the neuroanatomic substrate(s) mediating these effects remain unresolved. We hypothesized that the influence of opiates on sleep may be mediated, at least in part, by the ventrolateral preoptic nucleus (VLPO), a key cell group for producing behavioral sleep. By combining in situ hybridization for kappa and mu receptor mRNA with immunostaining of Fos expressed by VLPO cells during sleep we show that > 85% of sleep-active VLPO neurons contain mRNA for either or both opioid receptors. Microinfusions of a kappa receptor agonist into the VLPO region increased NREM sleep by 51% during the subjective night, whereas a mu receptor agonist increased wakefulness by 60% during the subjective day. The sleep- and wake-promoting effects of the kappa and mu agonists were blocked by prior administration of their respective antagonist. Combining retrograde tracing from the VLPO with immunohistochemistry for dynorphin (Dyn, the endogenous kappa receptor agonist) or endomorphin 1 (EM1, the endogenous mu receptor agonist) we show that the central lateral parabrachial subnucleus (PBcl) provides Dyn inputs to the VLPO, whereas hypothalamic histaminergic neurons provide EM1 inputs to the VLPO. In summary, results from the present study suggest that central opioid inputs to the VLPO may play a role in sleep–wake regulation and that the VLPO likely mediates the hypnotic response to high levels of opioid analgesics.

Journal

Brain ResearchElsevier

Published: Dec 15, 2008

References

  • Opposite modulation of histaminergic neurons by nociceptin and morphine
    Eriksson, K.S.; Stevens, D.R.; Haas, H.L.
  • Cellular neurophysiological actions of nociceptin/orphanin FQ
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  • Central pathways controlling brown adipose tissue thermogenesis
    Morrison, S.F.
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    Szymusiak, R.; Alam, N.; Steininger, T.L.; McGinty, D.
  • Waking selective neurons in the posterior hypothalamus and their response to histamine H3-receptor ligands: an electrophysiological study in freely moving cats
    Vanni-Mercier, G.; Gigout, S.; Debilly, G.; Lin, J.S.
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    Yakimova, K.S.; Sann, H.; Pierau, F.K.
  • A comparison between spontaneous electroencephalographic activities induced by morphine and morphine-related environment in rats
    Zuo, Y.F.; Wang, J.Y.; Chen, J.H.; Qiao, Z.M.; Han, J.S.; Cui, C.L.; Luo, F.

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