title: Intranasally applied L-DOPA alleviates parkinsonian symptoms in rats with unilateral nigro-striatal 6-OHDA lesions.
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.
authors: Center for Behavioral Neuroscience, University of Düsseldorf, Universitaetstrasse 1, 40225 Düsseldorf, Germany.
authors: Owen Y
authors: OY
authors: Chao
authors: Claudia
authors: C
authors: Mattern
authors: Angelica M De Souza
authors: AM
authors: Silva
authors: Janet
authors: J
authors: Wessler
authors: Lucia A
authors: LA
authors: Ruocco
authors: Susanne
authors: S
authors: Nikolaus
authors: Joseph P
authors: JP
authors: Huston
authors: Martin E
authors: ME
authors: Pum
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000281:Administration, Intranasal; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D001545:Benserazide / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004563:Electrochemistry; D005106:Exploratory Behavior / Q000187:drug effects; D005552:Forelimb / Q000502:physiology; D007839:Functional Laterality / Q000187:drug effects* / Q000502:physiology; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D016627:Oxidopamine / Q000009:adverse effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D013565:Sympatholytics / Q000009:adverse effects
chemical_list: D000978:Antiparkinson Agents; D013565:Sympatholytics; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D001545:Benserazide; D016627:Oxidopamine; D000661:Amphetamine; D004298:Dopamine; D006719:Homovanillic Acid