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. 2013 Dec 1;36(12):1777. doi: 10.5665/sleep.3194

Relation of Melanin Concentrating Hormone Levels to Sleep, Emotion and Hypocretin Levels

Ashley M Blouin 1, Jerome M Siegel 2,✉
PMCID: PMC3825424  PMID: 24293749

We thank the editor1 and commentators2–5 for their kind remarks on our human microdialysis paper6 and for integrating the results of all three papers.6–8 Our findings in the human are quite compatible with Konadhode et al.7 They found that optogenetic activation of MCH neurons decreased sleep onset latency and increased total sleep time. We see a great increase in MCH levels in the human brain at sleep onset and a smaller elevation of MCH levels throughout sleep. These microdialysis data together with Konadhode et al.'s stimulation data establish a causal link between MCH release and normal human sleep. In contrast, we see that Hcrt level, assessed from the same aliquots of microdialysis fluid, decreases prior to sleep onset. We agree with the commentators' suggestion that our findings of elevated MCH level after eating may be related to postprandial relaxation, although this increase is clearly occurring in a waking state and may simply be linked to satiety.

An important finding of our study was that whereas MCH and Hcrt are often inversely related to each other, this is not always the case. For example, MCH and Hcrt levels were both markedly decreased while the subjects were experiencing pain during waking. We found a strong link between Hcrt release and emotion, especially positive emotion. No such emotional link was seen with MCH levels with the same assays in the same aliquots. These unique human data thus highlight another difference between MCH and Hcrt: Hcrt is strongly related to positive affect, whereas MCH is not related to positive or negative affect within waking, but rather to sleep onset and satiation or postprandial relaxation.

We directly addressed the role of Hcrt neurons in a wide range of behaviors in prior studies in the dog, cat, rat, and mouse.9–14 These studies all point to a role for Hcrt in maintaining arousal during positively motivated behaviors such as play or bar pressing for food or water. Our human data are consistent with that conclusion.

CITATION

Blouin AM; Siegel JM. Relation of melanin concentrating hormone levels to sleep, emotion and hypocretin levels. SLEEP 2013;36(12):1777.

DISCLOSURE STATEMENT

This was not an industry supported study. The authors have indicated no financial conflicts of interest.

Footnotes

A response to Fraigne JJ, Peever JH, Jones BE, Hassani OK, McGinty D, Alam N, Luppi PH, Peyron C, and Fort P. Critical Topics Forum. Sleep 2013;36:1767–1776.

REFERENCES

  • 1.Szymusiak R. New insights into melanin concentrating hormone and sleep: a critical topics forum. Sleep. 2013;36:1765–6. [Google Scholar]
  • 2.Fraigne JJ, Peever JH. Melanin-concentrating hormone neurons promote and stabilize sleep. Sleep. 2013;36:1767–8. doi: 10.5665/sleep.3186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Jones BE, Hassani OK. The role of Hcrt/Orx and MCH neurons in sleep-wake state regulation. Sleep. 2013;36:1769–72. doi: 10.5665/sleep.3188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.McGinty D, Alam N. MCH neurons: the end of the beginning. Sleep. 2013;36:1773–4. doi: 10.5665/sleep.3190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Luppi PH, Peyron C, Fort P. Role of MCH neurons in paradoxical (REM) sleep control. Sleep. 2013;36:1775–6. doi: 10.5665/sleep.3192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Blouin AM, Fried I, Wilson CL, et al. Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction. Nat Commun. 2013;4:1547. doi: 10.1038/ncomms2461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Konadhode RR, Pelluru D, Blanco-Centurion C, et al. Optogenetic stimulation of MCH neurons increases sleep. J Neurosci. 2013;33:10257–63. doi: 10.1523/JNEUROSCI.1225-13.2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Jego S, Glasgow SD, Herrera CG, et al. Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus. Nat Neurosci. 2013 Aug 22; doi: 10.1038/nn.3522. [Epub ahead of print] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Kiyashchenko LI, Mileykovskiy BY, Maidment N, et al. Release of hypocretin (orexin) during waking and sleep states. J Neurosci. 2002;22:5282–6. doi: 10.1523/JNEUROSCI.22-13-05282.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.McGregor R, Wu M-F, Barber G, Ramanathan L, Siegel JM. Highly specific role of hypocretin (orexin) neurons: differential activation as a function of diurnal phase, operant reinforcement vs. operant avoidance and light level. J Neurosci. 2011;31:15455–67. doi: 10.1523/JNEUROSCI.4017-11.2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Mileykovskiy BY, Kiyashchenko LI, Siegel JM. Behavioral correlates of activity in identified hypocretin/orexin neurons. Neuron. 2005;46:787–98. doi: 10.1016/j.neuron.2005.04.035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Wu MF, John J, Maidment N, Lam HA, Siegel JM. Hypocretin release in normal and narcoleptic dogs after food and sleep deprivation, eating, and movement. Am J Physiol Regul Integr Comp Physiol. 2002;283:R1079–86. doi: 10.1152/ajpregu.00207.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Wu MF, Nienhuis R, Maidment N, Lam HA, Siegel JM. Role of the hypocretin (orexin) receptor 2 (Hcrt-r2) in the regulation of hypocretin level and cataplexy. J Neurosci. 2011;31:6305–10. doi: 10.1523/JNEUROSCI.0365-11.2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Wu MF, Nienhuis R, Maidment N, Lam HA, Siegel JM. Cerebrospinal fluid hypocretin (orexin) levels are elevated by play but are not raised by exercise and its associated heart rate, blood pressure, respiration or body temperature changes. Arch Ital Biol. 2011;149:492–8. doi: 10.4449/aib.v149i4.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]

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