Understanding habitual reward-seeking for addiction researchers

Habitual reward-seeking is one theory behind the persistence of substance use even in the presence of punishing consequences. Drug seeking can driven by environmental cues that signal potential drug availability as opposed the the presence of the drug itself. Addiction researchers are interested in how learned reward predictive cues can influence reward-seeking behavior even in the absence of reward. My team and I utilized rigourous A/B testing and neuroimaging to assess if subjects, and a specific brain target, still respond to reward-predictive cues even when the reward is omitted. We found that even in the absence of reward, habitual cue-induced reward-seeking and persistent brain target responses occur . This work supports further probing of this brain target and its causal role in habitual behavioral responses to drug-paired environmental cues. This work was funded by the National Institute on Drug Abuse.

problem

What is the human problem motivating addiction researchers?

  • Relapse is a common issue resulting in overdose, and environmental cues seem to play a major role in initiating drug-seeking that leads to relapse.

  • Novel understanding of cue-induced relapse is of interest so researchers can develop better interventions to prevent substance use relapse and subsequent illness and/or death.

What are the barriers addiction researchers are facing and how can we help?

  • Environmental cues are powerful modulators of drug-seeking behaviors, however, researchers have yet to identify the neural basis for habitual responding to reward-paired cues and if this neural basis is a reasonable target for intervention of substance use disorders.

goals

Determine how learned reward-predictive cues influence habitual reward-seeking actions when reward is absence.

  • determine if subjects respond to reward-predictive cues even when reward is absent.

  • determine if brain target activity is sensitive to absence of reward.

  • assess effect of intermittent absence of reward (A/B testing) vs. complete absence of reward (extinction).

approach

Use behavioral A/B testing, extinction and neuroimaging to determine the influence of habitual cue-responding on reward-seeking neural circuitry and behavioral outputs.

  • Use pseudo-random shuffling of reward and non-reward trials across subjects to see how behavioral measures change.

  • Use an extinction behavioral paradigm for all subjects to see how behavioral measures change.

  • Use neuroimaging to record brain target activity during A/B testing and extinction.

results

  • Subjects maintain their learned cue-induced reward-seeking during intermittent reward omission.

  • Subjects decrease their reward-seeking during full reward omission, however, maintain a 40% reward-seeking response rate even after days reward omission.

  • Brain target maintains learned neural responses to cues and behavioral outputs during intermittent reward omission

  • Brain target decreases neural response during full reward omission, however, maintains a significant amount of activity even after days of reward omission.

benefits

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