Intranasally applied l-DOPA alleviates parkinsonian symptoms in rats with unilateral nigro-striatal 6-OHDA lesions
Journal
Brain Research Bulletin
Series/Report No.
Brain Research Bulletin
Journal Volume
87
Journal Issue
2-3
Start Page
340-345
ISSN
0361-9230
Date Issued
2012-02
Author(s)
Mattern, Claudia
De Souza Silva, Angelica M.
Weßler, Janet
Ruocco, Lucia A.
Nikolaus, Susanne
Huston, Joseph P.
Pum, Martin E.
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 10-20 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.
SDGs
Publisher
Elsevier BV
Type
journal article