A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states

Jeroen P H Verharen, Johannes W de Jong, Theresia J M Roelofs, Christiaan F M Huffels, Ruud van Zessen, Mieneke C M Luijendijk, Ralph Hamelink, Ingo Willuhn, Hanneke E M den Ouden, Geoffrey van der Plasse, Roger A H Adan, Louk J M J Vanderschuren

Research output: Contribution to journal/periodicalArticleScientificpeer-review

207 Downloads (Pure)


Hyperdopaminergic states in mental disorders are associated with disruptive deficits in decision making. However, the precise contribution of topographically distinct mesencephalic dopamine pathways to decision-making processes remains elusive. Here we show, using a multidisciplinary approach, how hyperactivity of ascending projections from the ventral tegmental area (VTA) contributes to impaired flexible decision making in rats. Activation of the VTA-nucleus accumbens pathway leads to insensitivity to loss and punishment due to impaired processing of negative reward prediction errors. In contrast, activation of the VTA-prefrontal cortex pathway promotes risky decision making without affecting the ability to choose the economically most beneficial option. Together, these findings show how malfunction of ascending VTA projections affects value-based decision making, suggesting a potential mechanism through which increased forebrain dopamine signaling leads to aberrant behavior, as is seen in substance abuse, mania, and after dopamine replacement therapy in Parkinson's disease.

Original languageEnglish
Article number731
JournalNature Communications
Issue number1
Publication statusPublished - 2018


  • Journal Article


Dive into the research topics of 'A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states'. Together they form a unique fingerprint.

Cite this