Abstract
RationaleImpulsive behavior is a deleterious component of a number of mental health disorders but has few targeted pharmacotherapies. One contributing factor to the difficulty in understanding the neural substrates of disordered impulsivity is the diverse presentations of impulsive behavior. Defining the behavioral and cognitive processes which contribute to different subtypes of impulsivity is important for understanding the neural underpinnings of dysregulated impulsive behavior.MethodsUsing a mouse model for disordered impulsivity, our goal was to identify behavioral and cognitive processes that are associated with increased impulsivity. Specifically, we were interested in the facets of impulsivity modulated by serotonin signaling. We used mice lacking the serotonin 1B receptor (5-HT1BR) and measured different types of impulsivity as well as goal-directed responding, extinction, habitual-like behavior, cue reactivity, and reward reactivity.ResultsMice lacking expression of 5-HT1BR had increased levels of impulsive action, goal-directed responding, and motivation, with no differences seen in rate of extinction, development of habitual behavior, delay discounting, or effort-based discounting. Interestingly, mice lacking 5-HT1BR expression also showed an overall increase in the choice of higher value rewards, increased hedonic responses to sweet rewards, and responded more for cues that predict reward. We developed a novel paradigm to demonstrate that increasing anticipated reward value could directly increase impulsive action. Furthermore, we found that 5-HT1BR KO-induced impulsivity could be ameliorated by decreasing the reward value relative to controls, suggesting that the increased 5-HT1BR-associated impulsive action may be a result of increased reward valuation.ConclusionsTaken together, these data show that the effects of serotonin on impulsive action are mediated through the modulation of hedonic value, which may alter the reward representations that motivate action. Overall, this data supports a role for reward value as an important substrate in impulsive action which may drive clinically relevant increases in impulsivity.
Highlights
Impulsivity is an important component of daily life, but can lead to many deleterious outcomes such as making unhealthy eating decisions or excessive online shopping
Mice lacking 5-HT1BR expression showed increased responding on operant lever pressing including on random ratio and progressive ratio schedules, which was interestingly reversed by adult rescue of receptor expression
We show that 5-HT1BR expression influences goal-directed behavior, motivation, Pavlovian-toinstrumental transfer (PIT), and hedonic valuation, along with effects on impulsive action, but not impulsive choice
Summary
Impulsivity is an important component of daily life, but can lead to many deleterious outcomes such as making unhealthy eating decisions or excessive online shopping. It is a core component of a number of psychiatric disorders including attention deficit disorder, alcohol and substance use disorders, and gambling disorder (Dalley and Robbins 2017; MacKillop et al 2016; Robbins et al 2012). Treatment options to decrease impulsivity are limited, and those that exist are not targeted to impulsive behavior. One underlying issue in the development of approaches to reduce impulsive behavior lies within the complexity of the broad construct of impulsivity. Some argue against the use of the term impulsivity at all given the divergence and independence of its latent factors, in favor of more specific labels which have internally consistent
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