Levodopa administration modulates striatal processing of punishment-associated items in healthy participants

Abstract

Rationale

Appetitive and aversive processes share a number of features such as their relevance for action and learning. On a neural level, reward and its predictors are associated with increased firing of dopaminergic neurons, whereas punishment processing has been linked to the serotonergic system and to decreases in dopamine transmission. Recent data indicate, however, that the dopaminergic system also responds to aversive stimuli and associated actions.

Objectives

In this pharmacological functional magnetic resonance imaging study, we investigated the contribution of the dopaminergic system to reward and punishment processing in humans.

Methods

Two groups of participants received either placebo or the dopamine precursor levodopa and were scanned during alternating reward and punishment anticipation blocks.

Results

Levodopa administration increased striatal activations for cues presented in punishment blocks. In an interaction with individual personality scores, levodopa also enhanced striatal activation for punishment–predictive compared with neutral cues in participants scoring higher on the novelty-seeking dimension.

Conclusions

These data support recent indications that dopamine contributes to punishment processing and suggest that the novelty-seeking trait is a measure of susceptibility to drug effects on motivation. These findings are also consistent with the possibility of an inverted U-shaped response function of dopamine in the striatum, suggesting an optimal level of dopamine release for motivational processing.

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Acknowledgments

We thank Matthew Brett and Bertram Walter for support with data analysis and Sharwin Tafazoli for help with data acquisition. This research was supported by NIH grant DA02060.

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Correspondence to Bianca C. Wittmann.

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Wittmann, B.C., D’Esposito, M. Levodopa administration modulates striatal processing of punishment-associated items in healthy participants. Psychopharmacology 232, 135–144 (2015). https://doi.org/10.1007/s00213-014-3646-7

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Keywords

  • Reward
  • Punishment
  • Striatum
  • Levodopa
  • Novelty-seeking