EVALUATION OF LEVODOPA AND PRAMIPEXOLE COADMINISTRATION EFFECTS IN AN ANIMAL MODEL OF PARKINSON´S DISEASE

NEIMAN G; SABORIDO M; LARRAMENDY C; TARAVINI IRE; MURER MG; GERSHANIK OS

Cordoba

Congreso; I reunion Conjunta de Neurociencia; 2009

Sociedad Argentina de Investigacion en Neurociencia

Levodopa and dopamine agonists (DA) are currently available treatments for Parkinson’s disease. Levodopa is the most effective in alleviating motor disability but frequently induces dyskinesias, which may interfere with motor performance and reduce quality of life. DA have been proposed to have less induction of dyskinesias although they are not as effective as levodopa in the advanced stages of the disease. Our goal is to test if co-administration of levodopa and pramipexole, at doses that do not generate dyskinesias when used in monotherapy, has therapeutic effects without generation of dyskinesias. A levodopa doseresponse curve was performed on unilaterally 6-OHDA lesioned rats. Four weeks after the lesion, levodopa was orally administered at doses 6.25; 12.5 and 25 mg/kg during 10 days. Dyskinesias, turning behaviour and use of the contralateral forelimb were tested at day 1, 5 and 10. Tyrosine hydroxylase immunohistochemistry was performed to determine the degree of nigrostriatal dopaminergic system damage. We found that rats treated with levodopa 6.25 mg/kg did not develop dyskinesias whereas rats treated with 12.5 or 25 mg/kg did. The dose of pramipexole to be used in our co-administration experiments will be chosen based on previous results obtained in our laboratory. Once both doses are chosen, drugs will be orally administered together during 10 days and behavioural parameters will be tested. Our hypothesis is that co-administration of levodopa and pramipexole, at doses that fail to produce dyskinesias when used alone, should postpone the onset of dyskinesias and produce a synergistic effect capable of improving the use of the contralateral forelimb used as an index of therapeutic benefit.