Effects of repeated administration regimen of methyl levodopa on development of apomorphine sensitivity behavior in rats with unilateral 6-OHDA lesions

Effects of frequent, small doses of methyl levodopa on the development of dopaminergic sensitization were studied in an animal model of Parkinson's disease. Rats with 6-hydroxydopamine lesions of the left nigrostriatal dopaminergic pathway were first exposed i.p. to 25, 50, or 100 mg/kg methyl levodopa plus benserazide respectively every 12, 24, or 48 h, for 10 days. After a 7-day wash out period, the rats were given an s.c. injection of 0.05 mg/kg apomorphine which increased the number of contralateral rotations to the lesion side, evoked dystonic posture, or both. The rating score increases for apomorphine-induced abnormal behavior paralleled the larger individual doses and longer intervals of repeated methyl levodopa injection during the pre-exposure period. In dopamine-depleted animals, apomorphine sensitivity behavior may develop in association with the magnitude of and interval between pulsatile stimulation of dopamine receptors. Our finding supports the idea that frequent, small doses of levodopa may delay development of dopa-induced dyskinesia in parkinsonian patients.