Intranasally applied l-DOPA alleviates parkinsonian symptoms in rats with unilateral nigro-striatal 6-OHDA lesions

l-3,4-Dihydroxyphenylalanine (l-DOPA) remains the most effective drug for therapy of Parkinson's disease. However, the current clinical route of l-DOPA administration is variable and unreliable because of problems with drug absorption and first-pass metabolism. Administration of drugs via the nasal passage has been proven an effective alternate route for a number of medicinal substances. Here we examined the acute behavioral and neurochemical effects of intranasally (IN) applied l-DOPA in rats bearing unilateral lesions of the medial forebrain bundle, with severe depletion (97%) of striatal dopamine. Turning behavior in an open field, footslips on a horizontal grid and postural motor asymmetry in a cylinder were assessed following IN l-DOPA or vehicle administration with, or without, benserazide pre-treatment. IN l-DOPA without benserazide pre-treatment mildly decreased ipsilateral turnings and increased contralateral turnings 10–20 min after the treatment. IN l-DOPA with saline pre-treatment reduced contralateral forelimb-slips on the grid while no effects were evident in the cylinder test. These results support the hypothesis that l-DOPA can bypass the blood–brain barrier by the IN route and alleviate behavioral impairments in the hemiparkinsonian animal model.

► Acute effects of intranasally applied l-DOPA in hemiparkinsonian rats were examined. ► Intranasal l-DOPA administration reduced the forelimb slips on a horizontal grid. ► l-DOPA can bypass the blood-brain-barrier by the intranasal route.