Addictive substances like morphine and psychostimulants induce a preferential increase in dopamine (DA) output in the nucleus accumbens (NAC), a major terminal field of the mesolimbic dopaminergic projection. Two subregions of the NAC, the dorsolateral core and the ventromedial shell, are thought to subserve different functions related to the reinforcing properties of natural and drug rewards. The selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats, respectively, for rapid vs. extremely poor active avoidance acquisition in a shuttle-box has resulted in two phenotypes that differ in their behavioural and neurochemical responses to addictive drugs. We used brain dialysis to assess whether such differences in the responsiveness to drugs of abuse are related to differences in mesolimbic DA neuron function. In RHA rats, morphine, cocaine, and amphetamine caused a larger increase in DA efflux in the NAC shell vs. the NAC core, whereas the profile for the drug-induced increases in DA output was almost completely superimposable in the NAC shell and NAC core of RLA rats. Moreover, morphine, cocaine, and amphetamine caused a larger increment in basal DA output in the NAC shell of RHA rats vs. the NAC shell of RLA rats. These drugs also elicited a more robust increase in locomotion, rearing, sniffing, and grooming in RHA than in RLA rats. These results demonstrate that genetically determined differences in the functional properties of DA neurons projecting to the NAC shell may critically influence the behavioural response patterns to addictive drugs that distinguish the Roman lines.