Recent theories of drug dependence propose that the transition from occasional recreational substance use to harmful use and dependence results from the impact of disrupted midbrain dopamine signals for reinforcement learning on frontal brain areas that implement cognitive control and decision-making. We investigated this hypothesis in humans using electrophysiological and behavioral measures believed to assay the integrity of midbrain dopamine system and its neural targets. Our investigation revealed two groups of dependent individuals, one characterized by disrupted dopamine-dependent reward learning and the other by disrupted error learning associated with depression-proneness. These results highlight important neurobiological and behavioral differences between two classes of dependent users that can inform the development of individually tailored treatment programs.
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