Putting \u27Dopamine Overdose\u27 To The Test: A Psychopharmacological Investigation in Parkinson\u27s Disease and Healthy Volunteers

Dopaminergic therapy prescribed to address motor symptoms in Parkinson’s disease (PD) is done at the expense of some cognition functions. It has been hypothesized that whether a given function is improved or impaired by medication depends on the baseline dopamine levels within underlying brain regions. Areas most affected by PD and severely dopamine depleted are predicted to benefit from dopaminergic therapy. Regions with less dopamine deficiency are predicted to worsen from excessive dopamine stimulation. This theoretical framework is known as the dopamine overdose hypothesis. The central aim of this thesis was to critically test the straightforward predictions put forward by this overdose account. First, I examined the effects of dopaminergic therapy on stimulus-reward and reversal learning in groups of PD patients that differed in severity of their disease and extent of dopamine deficiency. Learning impairments were found in late-stage PD at baseline and in early-stage PD with dopaminergic therapy, replicating previous findings. Predicted medication-related improvements in late-stage PD were not found, however. Next, I tested the effects of a dopamine challenge with L-dopa on reward learning in groups of healthy volunteers differentially affected by age-related dopamine decline. I found age- related baseline learning impairments in older compared to younger adults. L- dopa worsened learning similarly in both age groups, however. Last, I explored the effects of L-dopa on learning and associated brain activity in a sample of healthy young volunteers who are presumed to have optimal endogenous dopamine levels. Learning and associated brain activity was reduced following L-dopa administration, but decision enactment was unaffected. Taken together, these studies provide partial support for the dopamine overdose hypothesis but suggest a less straightforward scenario than initially predicted