Melanin‐Concentrating Hormone (MCH) Decreases the Hypercapnic Ventilatory Response by Acting in the Lateral Hypothalamic Area (LHA)

Abstract

MCH plays an inhibitory role in the central hypercapnic chemoreflex, but the mechanisms were unclear so far. In this study, we tested the hypothesis that MCH1‐R receptors activation in LHA and/or Locus coeruleus (LC) is involved in the modulation of hypercapnic ventilatory response during the sleep/wake cycle. To do this, we measured pulmonary ventilation (VE), body temperature, EEG and EMG of unanesthetized male Wistar rats before and after microinjection of the MCH agonist (MCH, 0.4 mM) into the LHA and LC, or the MCH1‐R antagonist (SNAP‐94847; 63 mM), into the LHA, in room air and in 7% CO2 during wakefulness and sleep, in the dark and light periods. MCH intra‐LHA decreased the CO2 ventilatory response by 27% during wakefulness (VE = 1923 ± 384; n = 7 versus 2645 ± 293 mL kg‐1 min‐1; n = 6; P < 0.0001) and 16% during sleep (VE = 1914 ± 228; n = 6 versus2273 ± 243 mL kg‐1 min‐1; n = 4; P < 0.005) in the light, but not in the dark period while SNAP‐94847 intra‐LHA caused an increased CO2 ventilatory response during wakefulness in the light period, compared with the control group (VE = 2547 ± 277; n = 6 versus 2106 ± 329 mL kg‐1 min‐1; n = 6; P < 0.05). In the LC, MCH caused no change in the hypercapnic ventilatory response of rats. Our results suggest that MCH via MCH1‐R in the LHA, but not in the LC, exerts an inhibitory modulation of the hypercapnic ventilatory response during the light‐inactive period in rats.