Energetic responses are triggered by caudal brainstem melanocortin receptor stimulation and mediated by local sympathetic effector circuits

The central melanocortin system is a critical contributor to energy balance control. Melanocortin receptors (MC-Rs) are widely distributed throughout forebrain and caudal brainstem nuclei. To assess the contribution of hindbrain MC-Rs to the control of energy expenditure, the MC3/4R agonist melanotan II (MTII) was delivered to either the fourth ventricle or medullary raphe of neurologically intact rats and chronic decerebrate (CD) rats, and interscapular brown adipose tissue (IBAT) temperature (T_IBAT), core temperature (T_C), heart rate (HR), and spontaneous activity were recorded. Fourth ventricular MTII (0.1, 1.0 nmol) significantly increased T_IBAT, T_C, and HR in intact rats (T_C: +0.33 ± 0.08, +0.41 ± 0.09 C; HR: +40.84 ± 7.29, +69.04 ± 6.83 beats per minute) and in CDs (T_C: +1.39 ± 0.67, +1.52 ± 0.37 C; HR: +83.21 ± 19.2, +107.38 ± 17.65 beats per minute). Response magnitude was greater in CD rats than in neurologically intact rats. T _IBAT, T_C, and HR were significantly increased after 10 pmol MTII delivery to the medullary raphe of intact rats, and here too, the response magnitude was greater in decerebrate rats. The hyperthermia, IBAT thermogenesis, and tachycardia observed in CD rats after fourth ventricular and hindbrain parenchymal MTII injections support the hypothesis that hindbrain MC-R stimulation engages endemic circuits that link sympathetic outflows to thermogenic and cardiac effectors, and that forebrain processing and forebrain-caudal brainstem communication are not required for response production.