CARS encodes cysteinyl-tRNA synthetase, an enzyme that catalyzes the addition of cysteine to its cognate tRNA (Davidson et al., 2001) (Fig. 1 and Table 3). There is potential functional evidence that CARS plays a role in the addiction cycle. The thiol group on cysteine is highly nucleophilic and is easily oxidized into cystine. Due to its high reactivity it plays a role in many biological functions, most importantly as a mediator of the cellular redox state which mediates oxidative stress. The mammalian genome encodes approximately 214,000 cysteine residues of which at least 10–20% are redox sensitive under biologic conditions. Protection against oxidative stress by cysteine is partially mediated by glutathione (GSH), a highly abundant peptide formed from cysteine, glutamic acid and glycine. Chronic alcohol is well known to produce reactive oxygen species which plays a major role in neurodegeneration. Neurodegeneration is mediated in part by a reduction in cysteine containing GSH in human alcoholic brain and in binge drinking mice (Marballi et al., 2016; Wrona et al., 1997). In addition, increased glutamatergic excitatory signaling within corticostriatal pathways is associated with
