As our previous studies showed that MS activates an LH–LHb pathway to inhibit the mesolimbic DA system and cocaine addiction–like behaviors (Chang et al., 2017; Ahn et al., 2021; Lee et al., 2022), we hypothesized that the MS effects on cocaine addiction–like behaviors may be mediated via an orexinergic pathway from the LH to the LHb. Here, PLOD1 is linked to cocaine dependence.