Expression profile of dopamine agonists in an animal model of parkinsonism

CELIA LARRAMENDY; MARIANO SABORIDO; IRENE TARAVINI; GUSTAVO MURER; OSCAR GERSHANIK

Tandil, Argentina

Congreso; Cuadragésima Reunión Anual de la Sociedad Argentina de Farmacología Experimental.; 2008

Sociedad Argentina de Farmacilogía 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;} --> L-dopa and dopamine agonists (DA) are treatments available for Parkinson’s disease. L-dopa is the most effective to alleviate motor disability but induces dyskinesias. DA have been proposed to have neuroprotective effects and less induction of dyskinesias. Rats were injected with 6-OHDA in the left striatum and a partial and homogeneous striatal lesion was characterized. After surgery, animals were treated with L-dopa, pramipexole at doses that produced similar therapeutic benefit. A control group received vehicle alone. The therapeutic benefit was determined by the reversal of akinesia of the contralateral forepaw, induced by the lesion, and evaluated with the cylinder test. Three independent groups of normal and lesioned rats will be analyzed by microarray technology in order to compare the genetic profile of the groups: normal/vehicle, lesioned/vehicle, lesioned/levodopa, and lesioned/pramipexole. Within the profiles thus expressed we hope to identify transcripts related to the therapeutic effects, as well as those possibly related to neuroprotection, plasticity and dyskinesias. We hope to be able to speculate on the possible underlying mechanisms and their relationship with the pharmacodynamic and pharmacokinetic properties of the drugs under study.