The missing, the short, and the long: Levodopa responses and dopamine actions
The complex basic science literature on striatal dopamine suggests several important components of its actions.1 Disruption of striatal dopaminergic signaling should manifest in complex ways, and it should be possible to correlate important features of the clinical response to DRT with basic aspects of striatal dopaminergic signaling. The goal of this Grand Rounds is to explore these potential correlations to assist identification of mechanisms relevant to the clinical actions of DRT. Similarly, failures of our present understanding of dopaminergic nigrostriatal signaling to explain important features of DRT clinical pharmacology point to important areas for future investigation. We suggest that disruption of 3 key functions of striatal dopaminergic signaling—phasic dopaminergic signaling, permissive‐paracrine dopaminergic modulation of corticostriate synaptic plasticity, and tonic dopaminergic signaling that estimates the background rate of reward—explain important features of DRT clinical pharmacology. These potential correlations expose significant gaps between DRT clinical pharmacology and our present knowledge of dopaminergic nigrostriatal signaling.