HCRT and obesity due to melanocortin 4 receptor deficiency: Several investigations have focused on understanding how orexin neurons send output signals to multiple brain regions, such as the VTA and dorsal raphe nucleus, to regulate food intake, drug abuse, and energy homeostasis.[37, 38] Orexin signaling in the VTA gates morphine‐induced synaptic plasticity and CPP,[20, 39] while conversely, DA regulates excitatory transmission to orexin neurons in diet‐induced obesity.[40] Nevertheless, whether and how orexin neurons, regulated by the VTA reward system, are involved in feeding behavior under chronic morphine treatment remains unclear.