Motor temporal patterns and stereotypies but not rotational behavior can better explain motor response complications in Parkinson's disease.

DELFINO MA; STEFANO AV; FERRARIO JE; TARAVINI IR; MURER MG; GERSHANIK OS

Miami, Florida, USA

Congreso; 7th International Congress of Parkinson's Disease and Movement Disorders; 2002

The Movement Disorder Society

Objetives: To evaluate an experimental paradigm that could be used to challenge the hypothesis that rotational behavior is an indicator of L-dopa-induced dyskinesias. Background: Repeated treatment with dopamine agonists strongly potentiates contralateral turning behavior in response to D1 and D2 agonist in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats in the middle forebrain bundle (MFB). This sensitization is believed to be related  to motor response complications (dyskinesias, on-off states) that occur during chronic administration of L-DOPA in Parkinson's disease (PD) patients. Most authors conclude that the observed enhancement in rotational response after repeated L-Dopa or Apomorphine (Apo) administration is the experimental equivalent of L-Dopa induced dyskinesia (LID) seen in PD patients. However, there is evidence that 6-OHDA lesioned rats treated for 6 months with L-Dopa do not show a sensitized response, in terms of rotational behavior, to apomorphine injections, as it would have been expected. Moreover, given the rich repertoire of behaviors exhibited by rodents it is probably that they could display movements comparatively similar to the abnormal involuntary movements seen in PD patients under chronic L-Dopa treatment.. Methods: Animals were lesioned with 6-OHDA in the MFB. Two weeks later a cylinder test (% akinesia of the lesioned paw) was performed for the selection of the denervated animals. Animals were divided into three groups, one was primed with Apo, the second with quinpirole (Qp) and the third with vehicle; a month later treatment with Qp or Apo (for three weeks) was started and rotational behavior was observed and an abnormal involuntary movement test (AIM) was performed for two hours in each behavioral session. Inmunohistochemistry for c-fos was done in order to obtain a biochemical correlation. Results: We found that stereotypies and motor temporal patterns best distinguished between the different treatment regimes, while enhancement in rotational behavior did not differ significantly across groups. Selective increase in contralateral forepaw dyskinesia was highly expressed in Apo-Apo treated animals, followed by Apo-Qp, Qp-Qp, and vehicle. In addition the slope of the curve representing changes in rotation along time also showed differences between groups. Conclusion: We believe this simple evaluation paradigm could be used to differentiate drugs less prone to induce motor complications in Parkinson's Disease and provide an insight into their pathophysiology.