The
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated primate model of
Parkinson's disease provides a unique opportunity to study factors influencing the onset and persistence of
dyskinesia induced by
levodopa or
dopamine agonist treatment. Contrary to popular belief,
denervation is not essential for the induction of
dyskinesia, and both D1 and D2
dopamine agonist drugs are able to initiate dyskinetic movements. However, their ability to do so is currently attributed to their pharmacokinetic and pharmacodynamic properties rather than to their receptor selectivity, although this view is challenged in this article. Short-acting pulsatile
dopamine agonists are more likely to induce
dyskinesia than drugs that have a long duration of effect and produce continuous receptor stimulation. The induction of
dyskinesia does not seem to be associated with any obvious change in the number or sensitivity of post-synaptic
dopamine receptors, but rather to downstream events associated with the indirect and direct output pathways. Currently, there is evidence for the involvement of both pathways in the genesis of
dyskinesia and so there is no clear explanation for the onset of
involuntary movements or for the priming process that initiates
dyskinesia. However, a variety of therapeutic strategies primarily related to the use of non-
dopaminergic agents may be able to prevent
dyskinesia from occurring, and the actions of neurotropic factors, such as glial-derived neurotropic factor, may be effective in reversing established
involuntary movements.