Abnormal involuntary movements can better explain motor response complications in Parkinson's disease.

STEFANO A; DELFINO MA; FERRARIO JE; TARAVINI IR; GERSHANIK OS

Tandil, Buenos Aires, Argentina

Congreso; XXXIV Reunión Anual de la Asociación Argentina de Farmacología Experimental; 2002

Asociación Argentina de Farmacología Experimental (SAFE)

Repeated treatment with dopamine agonists D1 and D2 strongly potentiates contralateral turning behavior 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 rotational behaviour can not represent the complex phenomenon of L-DOPA induced dyskinesia. In this work, we study the presence of c-FOS as a marker of striatal neural activation in 6-OHDA lesioned rats under different regimenes of dopamine agonists and correlate these differences with the behavioral data (Circling Behavior and Abnormal Involuntary Movements, AIM). Briefly, animals were divided into three groups, one was primed with Apo, the second with Qp and the third with vehicle; a month later treatment with Qp or Apo (for three weeks) was started and rotational behavior and an AIM test was observed for two hours in each behavioral session. We found that stereotypies and motor temporal patterns best distinguished between the different treatment regimes and these differences are correlated with the striatal expression of c-FOS. Meanwhile, enhancement in rotational behavior did not differ significantly across groups. 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.