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Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation

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Abstract

Rationale

Selective rapid eye movement sleep (REMS) deprivation using the platform-on-water (“flower pot”) method causes sleep rebound with increased REMS, decreased REMS latency, and activation of the melanin-concentrating hormone (MCH) expressing neurons in the hypothalamus. MCH is implicated in the pathomechanism of depression regarding its influence on mood, feeding behavior, and REMS.

Objectives

We investigated the effects of the most selective serotonin reuptake inhibitor escitalopram on sleep rebound following REMS deprivation and, in parallel, on the activation of MCH-containing neurons.

Methods

Escitalopram or vehicle (10 mg/kg, intraperitoneally) was administered to REMS-deprived (72 h) or home cage male Wistar rats. During the 3-h-long “rebound sleep”, electroencephalography was recorded, followed by an MCH/Fos double immunohistochemistry.

Results

During REMS rebound, the time spent in REMS and the number of MCH/Fos double-labeled neurons in the lateral hypothalamus increased markedly, and REMS latency showed a significant decrease. All these effects of REMS deprivation were significantly attenuated by escitalopram treatment. Besides the REMS-suppressing effects, escitalopram caused an increase in amount of and decrease in latency of slow wave sleep during the rebound.

Conclusions

These results show that despite the high REMS pressure caused by REMS deprivation procedure, escitalopram has the ability to suppress REMS rebound, as well as to diminish the activation of MCH-containing neurons, in parallel. Escitalopram caused a shift from REMS to slow wave sleep during the rebound. Furthermore, these data point to the potential connection between the serotonergic system and MCH in sleep regulation, which can be relevant in depression and in other mood disorders.

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Acknowledgments

This study was supported by TAMOP-4.2.1.B-09/1/KMR-2010-0001, the 6th Framework Program of the European Community LSHM-CT-2004-503474, and the Hungarian Science Research Foundation, OTKA A-08-1-2009-0050.

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Authors and Affiliations

  1. Department of Pharmacodynamics, Semmelweis University, 1089 Nagyvárad tér 4., Budapest, Hungary

    Zita Kátai, Csaba Ádori, Tamás Kitka, Szilvia Vas, Diána Kostyalik, László Tóthfalusi & György Bagdy

  2. Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1113 Karolina út 29., Budapest, Hungary

    Lajos Kalmár

  3. Neuromorphological Research Laboratory of the Semmelweis University and the Hungarian Academy of Sciences, 1094 Tűzoltó utca 58., Budapest, Hungary

    Miklós Palkovits

  4. Group of Neurochemistry, Hungarian Academy of Sciences, 1083, Budapest, Hungary

    György Bagdy

  5. Group of Neuropsychopharmacology, Hungarian Academy of Sciences, 1083, Budapest, Hungary

    György Bagdy

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  1. Zita Kátai
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  2. Csaba Ádori
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  3. Tamás Kitka
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  4. Szilvia Vas
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  6. Diána Kostyalik
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  7. László Tóthfalusi
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  9. György Bagdy
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Correspondence to György Bagdy.

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Kátai, Z., Ádori, C., Kitka, T. et al. Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation. Psychopharmacology 228, 439–449 (2013). https://doi.org/10.1007/s00213-013-3046-4

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  • DOI: https://doi.org/10.1007/s00213-013-3046-4

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