Chao OY, et al.
JournalBrain Res Bull. 2011 Nov 15. [Epub ahead of print]
Abstract
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 10-20min 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.
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