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Dopaminergic contributions to behavioral control under threat of punishment in rats

Journal article
Authors J. P. H. Verharen
M. C. M. Luijendijk
Ljmj Vanderschuren
Roger A. H. Adan
Published in Psychopharmacology
Volume 237
Pages 1769-1782
ISSN 0033-3158
Publication year 2020
Published at Institute of Neuroscience and Physiology, Department of Physiology
Pages 1769-1782
Language en
Keywords Rats, Dopamine, Impulsivity, Behavioral inhibition, Ventral tegmental, area, Prefrontal cortex, Ventral striatum, Fiber photometry, Chemogenetics, Immediate early gene expression, ventral tegmental area, nucleus-accumbens core, impulsive behavior, d-2, receptors, c-fos, involvement, reward, performance, neurons, activation, Neurosciences & Neurology, Pharmacology & Pharmacy, Psychiatry
Subject categories Clinical pharmacology


Rationale Excessive 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. Objectives To 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. Methods We 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. Results Using 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. Conclusions Together, 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.

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Utskriftsdatum: 2020-08-11