Contribution of melanin-concentrating hormone (MCH1) receptor to thermoregulation and sleep stabilization: Evidence from MCH1 (−/−) mice

Recent studies have explored the implication of melanin-concentrating hormone (MCH) in the process of vigilance states. The current experiments were carried out in mice lacking the MCH1 receptor (−/−) and wild-type (WT) littermates, to assess the role of MCH1 receptor in the regulation of sleep architecture, body temperature (BT) and locomotor activity (LMA) under normal condition and following a 1 h restraint stress at lights onset. Under baseline conditions, MCH1 (−/−) mice exhibited consistent changes in waking and sleeping time across the 24-h recording period. We found an increase in the amount of wakefulness (MCH1 (−/−) 680.1 ± 15.3 min vs. WT, 601.9 ± 18.1, p < 0.05) at the expense of total duration of non rapid eye movement (NREM) sleep (MCH1 (−/−) 664.1 ± 13.9 min vs. WT 750.1 ± 18.5, p < 0.05). Additionally, MCH1 (−/−) mice had a higher mean basal body temperature (MCH1 (−/−), 36.6 ± 0.1° C vs. WT, 36.0 ± 0.1 °C, p < 0.05), particularly during the light-resting period. Restraint stress resulted in an immediate increase in wakefulness with a concomitant reduction in NREM sleep and REM sleep in both genotypes, followed by a homeostatic rebound sleep. A concomitant long lasting increase in BT, independently of the behavioural state accompanied those changes in both genotypes. The elevated basal body temperature and reduction in NREM sleep time resulting from shorter NREM episode durations observed in MCH1 (−/−) suggests that central MCH1 receptor has a role in thermoregulation and presumably stabilization of NREM sleep.

Research highlights▶ MCH1r (−/−) mice exhibited increases body temperature and reduced NREM sleep time. ▶ Reduced NREM sleep by shorter NREM sleep episodes may impact sleep stabilization. ▶ Pharmacological blockade of MCH1r in rats support our findings in MCH1r (−/−) mice. ▶ MCH system and MCH1r have a role in the mechanisms underlying thermoregulation. ▶ MCH system and MCH1r may contribute to NREM sleep stabilization and consolidation.