Dopaminergic contributions to behavioral control under threat of punishment in rats

Jeroen P H Verharen,Mieneke C M Luijendijk,Roger A H Adan,Louk J M J Vanderschuren

doi:10.1007/s00213-020-05497-w

Abstract

RationaleExcessive intake of rewards, such as food and drugs, often has explicit negative consequences, including the development of obesity and addiction, respectively. Thus, choosing not to pursue reward is the result of a cost/benefit decision, proper execution of which requires inhibition of behavior. An extensive body of preclinical and clinical evidence implicates dopamine in certain forms of inhibition of behavior, but it is not fully known how it contributes to behavioral inhibition under threat of explicit punishment.ObjectivesTo assess the involvement of midbrain dopamine neurons and their corticostriatal output regions, the ventral striatum and prefrontal cortex, in control over behavior under threat of explicit (foot shock) punishment in rats.MethodsWe used a recently developed behavioral inhibition task, which assesses the ability of rats to exert behavioral restraint at the mere sight of food reward, under threat of foot shock punishment. Using in vivo fiber photometry, chemogenetics, c-Fos immunohistochemistry, and behavioral pharmacology, we investigated how dopamine neurons in the ventral tegmental area, as well as its output areas, the ventral striatum and prefrontal cortex, contribute to behavior in this task.ResultsUsing this multidisciplinary approach, we found little evidence for a direct involvement of ascending midbrain dopamine neurons in inhibitory control over behavior under threat of punishment. For example, photometry recordings suggested that VTA DA neurons do not directly govern control over behavior in the task, as no differences were observed in neuronal population activity during successful versus unsuccessful behavioral control. In addition, chemogenetic and pharmacological manipulations of the mesocorticolimbic DA system had little or no effect on the animals’ ability to exert inhibitory control over behavior. Rather, the dopamine system appeared to have a role in the motivational components of reward pursuit.ConclusionsTogether, our data provide insight into the mesocorticolimbic mechanisms behind motivated behaviors by showing a modulatory role of dopamine in the expression of cost/benefit decisions. In contrast to our expectations, dopamine did not appear to directly mediate the type of behavioral control that is tested in our task.

Highlights

Inhibitory control over behavior is a process that can help to limit the pursuit of rewards like food and drugs and thereby prevent the occurrence of explicit negative consequences that are associated with its excessive intake
To study the process of behavioral inhibition in the face of possible punishment, we recently developed a task that studies control over the intake of sucrose pellets in rats (Verharen et al 2019c)
DA neurons may encode reward or reward prediction errors (Schultz et al 1997; Schultz 2016), resulting in increased activity when animals can retrieve the pellet without punishment and possibly reduced DA neuron activity during stimulus onset

Summary

Introduction

Inhibitory control over behavior is a process that can help to limit the pursuit of rewards like food and drugs and thereby prevent the occurrence of explicit negative consequences that are associated with its excessive intake. To study the process of behavioral inhibition in the face of possible punishment, we recently developed a task that studies control over the intake of sucrose pellets in rats (Verharen et al 2019c). In this task, behavioral control is required during the presentation of an audiovisual threat signal, whereby an inability to resist eating the pellet during this threat signal is punished with a mild electric foot shock. The ventral striatum (VS) was important for the motivational aspects of behavior in this task (Verharen et al 2019c)

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