A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states

Nat Commun. 2018 Feb 21;9(1):731. doi: 10.1038/s41467-018-03087-1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Decision Making*
  • Dopamine / analysis
  • Dopamine / metabolism*
  • Humans
  • Male
  • Mental Disorders / metabolism*
  • Mental Disorders / physiopathology
  • Mental Disorders / psychology*
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiopathology
  • Rats
  • Rats, Wistar
  • Risk-Taking
  • Ventral Tegmental Area / metabolism
  • Ventral Tegmental Area / physiopathology


  • Dopamine