Dissociating the cognitive effects of levodopa versus dopamine agonists in a neurocomputational model of learning in Parkinson's disease

Background/Aims: Levodopa and dopamine agonists have different effects on the motor, cognitive, and psychiatric aspects of Parkinson's disease (PD). Methods: Using a computational model of basal ganglia (BG) and prefrontal cortex (PFC) dopamine, we provide a theoretical synthesis of the dissociable effects of these dopaminergic medications on brain and cognition. Our model incorporates the findings that levodopa is converted by dopamine cells into dopamine, and thus activates prefrontal and striatal D₁ and D₂ dopamine receptors, whereas antiparkinsonian dopamine agonists directly stimulate D ₂ receptors in the BG and PFC (although some have weak affinity to D₁ receptors). Results: In agreement with prior neuropsychological studies, our model explains how levodopa enhances, but dopamine agonists impair or have no effect on, stimulus-response learning and working memory. Conclusion: Our model explains how levodopa and dopamine agonists have differential effects on motor and cognitive processes in PD.