Mesolimbic dopamine neurons projecting from the ventral tegmental area to the nucleus accumbens (NAc) are part of a complex circuit mediating cocaine-directed behaviors. However, the precise role of rapid (subsecond) dopamine release within the primary subregions of the NAc (the core and shell) and its relationship to NAc cell firing during this behavior remain unknown. Here, using fast-scan cyclic voltammetry in rats we report rapid dopamine signaling in both the core and shell; however, significant differences were observed in the timing of dopamine release events within seconds of the cocaine-reinforced response during self-administration sessions. Importantly, simultaneous voltammetric and electrophysiological recordings from the same electrode reveal that, at certain sites within both subregions, neurons exhibiting patterned activation were observed at locations where rapid dopamine release was present; the greater the strength of the neural signal the larger the dopamine release event. In addition, it was at those locations that electrically-evoked stimulated release was greatest. No changes in dopamine were observed where nonphasic neurons were recorded. Thus, although differences are evident in dopamine release dynamics relative to cocaine-reinforced responding within the core and shell, dopamine release is heterogeneous within each structure and varies as a function of precise neuronal targets during cocaine-seeking behavior.