Melanin-concentrating hormone regulates the hypercapnic chemoreflex by acting in the lateral hypothalamic area

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide involved in a broad range of homeostatic functions including regulation of the hypercapnic chemoreflex. We evaluated whether MCH modulates the hypercapnic ventilatory response by acting in the lateral hypothalamic area (LHA) and/or in the locus coeruleus (LC). Here, we measured pulmonary ventilation (file:///C:/Users/mirel/AppData/Local/Temp/msohtmlclip1/01/clip_image002.gifE), body temperature, electroencephalogram (EEG) and electromyogram (EMG) of unanesthetized adult male Wistar rats before and after microinjection of MCH [0.4 mM] or MCH1-R antagonist (SNAP-94847 [63 mM]) into the LHA and LC, in room air and 7% CO2 conditions during wakefulness and sleep, in the dark and light periods. MCH intra-LHA caused a decreased CO2 ventilatory response during wakefulness and sleep in the light period, while SNAP-94847 intra-LHA increased this response, during wakefulness in the light period. In the LC, MCH or the MCH1-R antagonist caused no change in the hypercapnic ventilatory response. Our results suggest that MCH, in the LHA, exerts an inhibitory modulation of the hypercapnic ventilatory response during the light-inactive period in rats.