Recent work on the neuromodulatory regulation of LHb excitability and synaptic transmission by CRF/CRFR1 and Dyn/KOR signaling and their dysregulation by MD in male rats (Authement et al., 2018; Simmons et al., 2020) further highlight involvement of critical neuromodulators within LHb circuits that could underlie ELS-induced anhedonia, motivational deficits, drug seeking behaviors, and flexibility related behaviors. This evidence concerns the gene LHB and Menkes disease.