The report by Togasaki and colleagues, 1 which reported that levodopa could induce dyskinesias in normal squirrel monkeys, is of great interest. The investigators report that the administration of crushed tablets of Sinemet CR to normal monkeys resulted in the induction of what is described as levodopa-induced dyskinesias in every single monkey. As the authors point out, this is at odds with considerable literature that indicates that the administration of levodopa (L-DOPA) in experimental animals or in human beings who have an intact nigrostriatal dopaminergic system does not elicit such movements. [2][3][4] The investigators use the global primate dyskinesia rating scale to measure the dyskinesias and monitor motor activity of the animals in cages fitted with infrared activity sensors. Because dopaminergic agents (L-DOPA amphetamine, methylphenidate, apomorphine) are all known to elicit stereotyped mouthing movements at appropriate dosages in normal animals with associated decrease in locomotor activity, one wonders whether this finding in all six monkeys tested represents dopaminergic-induced stereotypy, rather than dyskinesias, as observed in patients with Parkinson's disease.
The authors propose that this model could serve as an important one for further understanding the biology of L-DOPA-induced dyskinesias. Obviously, these findings need to be replicated by an independent laboratory. Further more, the model that administration of L-DOPA for a short time (10 days) to normal monkeys induces something akin to L-DOPA-induced dyskinesias in patients with Parkinson's disease is questionable. The administration of L-DOPA to patients who do not have Parkinson's disease, and who presumably have a normal nigrostriatal system, as well as the administration of L-DOPA to patients with early Parkinson's disease and a damaged negrostriatal system, does not often result in L-DOPA-induced dyskinesias in such a remarkably short time.