Reward, interrupted: Inhibitory control and its relevance to addictions

•The inability to effortfully inhibit drug-seeking and -taking actions is central to addictions.•Impaired inhibitory control over motivated behaviors occurs as a consequence of drug experience.•Natively poor inhibitory control abilities predict addiction susceptibility.•Dopamine and serotonin, acting alone and in concert, influence inhibitory control.•Improving inhibitory control may be an important new approach for treating addictions.

There are broad individual differences in the ability to voluntarily and effortfully suppress motivated, reward-seeking behaviors, and this review presents the hypothesis that these individual differences are relevant to addictive disorders. On one hand, cumulative experience with drug abuse appears to alter the molecular, cellular and circuit mechanisms that mediate inhibitory abilities, leading to increasingly uncontrolled patterns of drug-seeking and -taking. On the other, native inter-individual differences in inhibitory control are apparently a risk factor for aspects of drug-reinforced responding and substance use disorders. In both cases, the behavioral manifestation of poor inhibitory abilities is linked to relatively low striatal dopamine D2-like receptor availability, and evidence is accumulating for a more direct contribution of striatopallidal neurons to cognitive control processes. Mechanistic research is now identifying genes upstream of dopamine transmission that mediate these relationships, as well as the involvement of other neurotransmitter systems, acting alone and in concert with dopamine. The reviewed research stands poised to identify new mechanisms that can be targeted by pharmacotherapies and/or by behavioral interventions that are designed to prevent or treat addictive behaviors and associated behavioral pathology.This article is part of a Special Issue entitled ‘NIDA 40th Anniversary Issue’.