As the directionality of the relationship between Cg-CPu circuit connectivity and escalating addiction-like behavior observed herein concur with that observed in the extant literature [37–39], this circuit has now repeatedly been demonstrated to have an inverse relationship with dependence behaviors across species (FTND score in humans and withdrawal severity score/escalation score in rats) and substances (nicotine and heroin). Here, CPB2 is linked to substance dependence.