The ventrolateral preoptic area (VLPO) has been recognized as one of the key structures responsible for the generation of non-REM (NREM) sleep. The melanin-concentrating hormone (MCH)-containing neurons, which are located in the lateral hypothalamus and incerto-hypothalamic area, project widely throughout the central nervous system and include projections to the VLPO. The MCH has been associated with the central regulation of feeding and energy homeostasis. In addition, recent findings strongly suggest that the MCHergic system promotes sleep. The aim of the present study was to determine if MCH generates sleep by regulating VLPO neuronal activity. To this purpose, we characterized the effect of unilateral and bilateral microinjections of MCH into the VLPO on sleep and wakefulness in the rat. Unilateral administration of MCH into the VLPO and adjacent dorsal preoptic area did not modify sleep. On the contrary, bilateral microinjections of MCH (100 ng) into these areas significantly increased light sleep (LS, 39.2 +/- 4.8 vs. 21.6 +/- 2.5 min, P < 0.05) and total NREM sleep (142.4 +/- 23.2 vs. 86.5 +/- 10.5 min, P < 0.05) compared to control (saline) microinjections. No effect was observed on REM sleep. We conclude that MCH administration into the VLPO and adjacent dorsal lateral preoptic area promotes the generation of NREM sleep. (C) 2012 Elsevier Inc. All rights reserved.
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Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo 1130033, Japan
Keio Univ, Grad Sch Pharmaceut Sci, Tokyo 1058512, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Tokyo 1130033, Japan
Yoshimoto, Airi
Yamashiro, Kotaro
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Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo 1130033, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Tokyo 1130033, Japan
Yamashiro, Kotaro
Suzuki, Takeshi
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Keio Univ, Grad Sch Pharmaceut Sci, Tokyo 1058512, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Tokyo 1130033, Japan
Suzuki, Takeshi
Ikegaya, Yuji
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Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo 1130033, Japan
Natl Inst Informat & Commun Technol, Ctr Informat & Neural Networks, Suita, Osaka 5650871, Japan
Univ Tokyo, Inst AI & Beyond, Tokyo 1130033, JapanUniv Tokyo, Grad Sch Pharmaceut Sci, Tokyo 1130033, Japan