Validation of the l-dopa-induced dyskinesia in the 6-OHDA model and evaluation of the effects of selective dopamine receptor agonists and antagonists

To study this issue, we have reproduced the l-dopa-induced dyskinesia model developed by Cenci et al. [M.A. Cenci, C.S. Lee, A. Bjorklund, l-DOPA-induced dyskinesia in the rat is associated with striatal overexpression of prodynorphin- and glutamic acid decarboxylase mRNA, Eur. J. Neurosci. 10 (1998) 2694-2706] in the rat. We find that their abnormal involuntary movements rating scale is easy to apply and consistent to use. Moreover, the Schallert forelimb placing test has been used to assess l-dopa-induced recovery of function and we find that the rats continue to show good recovery on this test, even while they are exhibiting abnormal dyskinetic side effects. To further evaluate this model, we have studied the effects of selective dopamine receptor antagonists and agonists for D1, D2 and D3 receptors. Antagonists of all three receptors are able to block the l-dopa-induced dyskinesia without interfering with the beneficial effects of l-dopa on the placing test. This indicates that the effects of chronic l-dopa on recovery of parkinsonian symptoms and on induction of dyskinetic side effects can be dissociated, which may provide the basis for developing novel combination treatments, e.g. using grafts while blocking the unwanted adverse effects of the drugs.