Levodopa administration modulates striatal processing of punishment-associated items in healthy participants
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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.
In this pharmacological functional magnetic resonance imaging study, we investigated the contribution of the dopaminergic system to reward and punishment processing in humans.
Two groups of participants received either placebo or the dopamine precursor levodopa and were scanned during alternating reward and punishment anticipation blocks.
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.
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.
KeywordsReward Punishment Striatum Levodopa Novelty-seeking
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.
- Clatworthy PL, Lewis SJG, Brichard L, Hong YT, Izquierdo D, Clark L, Cools R, Aigbirhio FI, Baron J-C, Fryer TD, Robbins TW (2009) Dopamine release in dissociable striatal subregions predicts the different effects of oral methylphenidate on reversal learning and spatial working memory. J Neurosci 29:4690–4696PubMedCrossRefGoogle Scholar
- Dang LC, O'Neil JP, Jagust WJ (2012) Genetic effects on behavior are mediated by neurotransmitters and large-scale neural networks. Neuroimage 66C:203–214Google Scholar
- Eckert T, Sailer M, Kaufmann J, Schrader C, Peschel T, Bodammer N, Heinze HJ, Schoenfeld MA (2004) Differentiation of idiopathic Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and healthy controls using magnetization transfer imaging. Neuroimage 21:229–235PubMedCrossRefGoogle Scholar
- Hutton C, Deichmann R, Turner R, Andersson JLR (2004) Combined correction for geometric distortion and its interaction with head motion in fMRI Proceedings of ISMRM 12, Kyoto, Japan, pp 1084Google Scholar
- Joshua M, Adler A, Mitelman R, Vaadia E, Bergman H (2008) Midbrain dopaminergic neurons and striatal cholinergic interneurons encode the difference between reward and aversive events at different epochs of probabilistic classical conditioning trials. J Neurosci 28:11673–11684PubMedCrossRefGoogle Scholar
- Kelly C, de Zubicaray G, Di Martino A, Copland DA, Reiss PT, Klein DF, Castellanos FX, Milham MP, McMahon K (2009) L-dopa modulates functional connectivity in striatal cognitive and motor networks: a double-blind placebo-controlled study. J Neurosci 29:7364–7378PubMedCentralPubMedCrossRefGoogle Scholar
- Penny W, Henson R (2007) Analysis of variance. In: Friston KJ, Ashburner J, Kiebel SJ, Nichols TE, Penny W (eds) Statistical parametric mapping: the analysis of functional brain images. Elsevier Academic Press, AmsterdamGoogle Scholar
- Schott BH, Minuzzi L, Krebs RM, Elmenhorst D, Lang M, Winz OH, Seidenbecher CI, Coenen HH, Heinze HJ, Zilles K, Duzel E, Bauer A (2008) Mesolimbic functional magnetic resonance imaging activations during reward anticipation correlate with reward-related ventral striatal dopamine release. J Neurosci 28:14311–14319PubMedCrossRefGoogle Scholar