D1 and D2 dopamine receptor antagonists effects on levodopa-induced dyskinesias.

SABORIDO MD; TARAVINI IR; LARRAMENDY C; MURER MG; GERSHANIK OS

Tandil, Buenos Aires, Argentina

Congreso; XL Reunión Anual de la Asociación Argentina de Farmacología Experimental; 2008

Asociación Argentina de Farmacología Experimental (SAFE)

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> A common and troublesome complication of L-dopa therapy in Parkinson’s disease is the development of L-dopa-induced dyskinesias (LID). To evaluate if it is possible to separate the generation of LID from the motor response induced by L-dopa, rats with severe lesion of the nigrostriatal pathway were treated during 12 days with L-dopa. Once LID were established, rats were treated with increasing doses of SCH-23390 (D1 antagonist) or raclopride (D2 antagonist) in order to obtain a dose that ameliorated LID without interfering with the motor response. We found that SCH-23390 at a dose >0.005mg/kg ameliorates the severity of LID. However, at these doses also the motor response evaluated by means of contralateral rotations were also reduced. On the other hand, we were not able to find a dose of raclopride that reduced the LID score induced by L-dopa. This was probably because of the very low doses used here. These data in part supports the idea that once dyskinesias are established it is not possible to separate its generation from the motor response induced by a L-dopa.