A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states

Verharen, J. P. H.; de Jong, J. W.; Roelofs, T. J. M.; Huffels, C. F. M.; van Zessen, R.; Luijendijk, M. C. M.; Hamelink, R.; Willuhn, I.; den Ouden, H. E. M.; van der Plasse, G.; Adan, R. A. H.; Vanderschuren, L. J. M. J.

doi:10.1101/211862

bioRxiv · 10.1101/211862

A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states

Verharen, J. P. H.·de Jong, J. W.·Roelofs, T. J. M.·Huffels, C. F. M.·van Zessen, R.·Luijendijk, M. C. M.·Hamelink, R.·Willuhn, I.·den Ouden, H. E. M.·van der Plasse, G.·Adan, R. A. H.·Vanderschuren, L. J. M. J.

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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 faulty 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, providing a mechanistic understanding of the reckless behaviors seen in substance abuse, mania, and after dopamine replacement therapy in Parkinsons disease.

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Verharen, J. P. H., de Jong, J. W., Roelofs, T. J. M., Huffels, C. F. M., van Zessen, R., Luijendijk, M. C. M., Hamelink, R., Willuhn, I., den Ouden, H. E. M., van der Plasse, G., Adan, R. A. H., Vanderschuren, L. J. M. J.. 2017-10-31. A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states. https://doi.org/10.1101/211862

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