Via targeting the NAc-projecting DA cells, orexin regulates reward seeking (Harris et al. 2005), cocaine self-administration (España et al. 2011), palatable food intake (Zheng et al. 2007), male sexual behavior (Muschamp et al. 2007), morphine withdrawal (Sharf et al. 2008) and controls the disinhibition of dopaminergic neurons in severe obesity (Tunisi et al. 2021). The gene discussed is HCRT; the disease is obesity due to melanocortin 4 receptor deficiency.