Presymptomatic compensation in Parkinson's disease is not dopamine-mediated

Trends Neurosci. 2003 Apr;26(4):215-21. doi: 10.1016/S0166-2236(03)00038-9.


The symptoms of Parkinson's disease (PD) appear only after substantial degeneration of the dopaminergic neuron system (e.g. an 80% depletion of striatal dopamine)--that is, there is a substantive presymptomatic period of the disease. It is widely believed that dopamine-related compensatory mechanisms are responsible for delaying the appearance of symptoms. Recent advances in understanding the presymptomatic phase of PD have increased our understanding of these dopamine-related compensatory mechanisms and have highlighted the role of non-dopamine-mediated mechanisms both within and outside the basal ganglia. This increased knowledge of plasticity within cortical-basal-ganglia-thalamocortical circuitry as dopaminergic neuron degeneration progresses has implications for understanding plasticity in neural circuits generally and, more specifically, for developing novel therapeutics or presymptomatic diagnostics for PD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological / physiology*
  • Animals
  • Basal Ganglia / physiopathology
  • Disease Progression
  • Dopamine / metabolism*
  • Enkephalins / genetics
  • Enkephalins / metabolism
  • Globus Pallidus / physiopathology
  • Humans
  • Models, Neurological
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology*
  • Receptors, Dopamine D2 / physiology
  • Substantia Nigra / physiopathology


  • Enkephalins
  • Receptors, Dopamine D2
  • Dopamine