Abstract
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.
Highlights
Hyperdopaminergic states in mental disorders are associated with disruptive deficits in decision making
The mesocorticolimbic system, comprising DA cells within the ventral tegmental area (VTA) that mainly project to the nucleus accumbens (NAc; mesoaccumbens pathway) and medial prefrontal cortex, has an important role in value-based learning and decision making[14,15,16]
When a reward does not fulfill expectations, DA neuronal activity decreases. This pattern of DA cell activity is the basis of reward prediction error (RPE) theory[17,18,19,20], which describes an essential mechanism through which organisms learn to flexibly alter their behavior when the costs and benefits associated with different courses of action shift
Summary
Hyperdopaminergic states in mental disorders are associated with disruptive deficits in decision making. 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. Our data show that activation of the VTA–NAc pathway reduces the sensitivity to loss and punishment as a result of impaired processing of negative RPEs, whereas activation of the VTA–mPFC pathway promotes risky decision making, but only when this entails no loss of reward Together, these findings shed light on the behavioral mechanisms by which increased activity of distinct ascending DA projections contributes to deficits in value-based decision-making processes
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