Elsevier

Neuropharmacology

Volume 76, Part B, January 2014, Pages 479-486
Neuropharmacology

Invited review
Reward, interrupted: Inhibitory control and its relevance to addictions

https://doi.org/10.1016/j.neuropharm.2013.05.022Get rights and content

Highlights

  • 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.

Abstract

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’.

Section snippets

Motivated actions and inhibition

Like food/nutrients, water and sexual stimuli, drugs of abuse act as behavioral reinforcers, and humans and non-human animals are motivated to obtain them (Brady, 1991; Johanson, 1978; Spealman and Goldberg, 1978; Weeks, 1962). Since the work of Olds and Milner in the 1950s (Olds and Milner, 1954), an immense amount has been learned about the neural pathways that mediate reinforcement and reward and that allow drugs of abuse to support seeking and taking behaviors (Gardner, 2011; Haber and

Inhibitory control deficits in addiction

It is well-established that addictions are associated with reduced inhibitory control (Ersche et al., 2011, 2008, 2012; Fillmore and Rush, 2002, 2006; Lee et al., 2009; Monterosso et al., 2005). These investigations involved the use of a variety of laboratory measures conventionally thought to measure inhibitory control over pre-potent or impulsive responses, including self-report measures of impulsivity (Patton et al., 1995), the stop signal reaction time task, multiple choice serial reaction

The neural circuitry of inhibitory control

Earlier models linking inhibitory control deficits to addiction proposed a central role for catecholamine transmitters in regulating frontostriatal circuits (Jentsch and Taylor, 1999). This hypothesis was supported by findings that substance dependent individuals displayed reduced prefrontal glucose utilization (Volkow et al., 1991, Volkow et al., 1992, Volkow et al., 1993), that damage to prefrontal regions in humans and animals resulted in disinhibited and perseverative behaviors (Butter, 1969

Dopamine

Medium spiny neurons of the striatum have canonically been divided into two populations: those of the striatonigral pathway that express dopamine D1 receptors and those of the striatopallidal pathway that express dopamine D2-like receptors (Gerfen et al., 1990). In line with imaging studies showing decreased striatal D2-like receptor availability in substance dependence, pharmacological and genetic studies have accentuated a role for striatopallidal neurons in inhibitory control. A study

Inhibitory control and process addictions

Mounting evidence suggests that inhibitory control deficits are not unique to addictions to drugs of abuse, but rather, may also play a role in process addictions, such as pathological gambling, compulsive overeating and/or sex addiction (Batterink et al., 2010; Blaszczynski et al., 1997; Cserjési et al., 2007; Jasinska et al., 2012; Leeman and Potenza, 2012; Steel and Blaszczynski, 1998; Verdejo-García et al., 2010; Vitaro et al., 1997). In light of the observation that inhibitory control

Conclusions

Over the past dozen years or so, the concept that inhibitory control abilities are crucial to conceptual models of addiction has become well accepted in the field. Moreover, its relationship to addictions – both as a susceptibility factor and mediator of the progressive transition from use, to abuse, to dependence – has also been well established. Important roles of dopamine D2-like and serotonin receptors have also been delineated. Nevertheless, much work remains to be done. Only recently have

Acknowledgments

The preparation of this article was supported, in part, by PHS grants R01-DA031852 (JDJ) and T32-DA024635 (Edythe London).

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