Physiology of the normal and dopamine-depleted basal ganglia: Insights into levodopa pharmacotherapy

Authors

  • Anthony A. Grace PhD

    Corresponding author
    1. Department of Neuroscience, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    2. Department of Psychiatry, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    3. Departments of Psychology, Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    • Department of Neuroscience, Center for Neuroscience, A210 Langley Hall, University of Pittsburgh, Pittsburgh, Pennsylvania 15260
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  • Potential conflict of interest: Nothing to report.

Abstract

Dopamine (DA) neurons exist in two activity states; either spontaneously firing or quiescent and nonfiring. When faced with a behavioral demand, the quiescent DA neurons can be activated to facilitate normal motor output. Levodopa appears to increase DA output by activating these nonfiring neurons; as a consequence, DA release is increased, but behavioral demand can now overwhelm the system, potentially leading to the inactivation and on/off phenomena. Levodopa administered in a pulsatile manner may also lead to the induction of synaptic plasticity within the DA systems. In the ventral mesolimbic system, this could lead to the loss of behavioral flexibility, impulsive behavior, and cognitive impairment, whereas in the dorsal nigrostriatal system, this may underlie Levodopa-induced dyskinesia. Continuous administration of Levodopa may circumvent this sensitization process, enabling a therapeutic response without limbic and motor side effects. © 2008 Movement Disorder Society

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