title: Dystonia is predictive of subsequent altered dopaminergic responsiveness in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine+3-nitropropionic acid model of striatonigral degeneration in monkeys.
abstract: We conducted a new chronic sequential 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3-nitropropionic acid (3NP) intoxication paradigm in two female monkeys in order to reproduce the striatonigral degeneration type of levodopa-unresponsive parkinsonism. A comparison was made with MPTP-, 3NP-intoxicated and control monkeys. A levodopa-responsive parkinsonism emerged in all MPTP-treated monkeys. During subsequent 3NP intoxication, one of the two MPTP +3NP monkeys exhibited hindlimb dystonia concomitantly with a reduced levodopa response. All MPTP-monkeys had severe cell loss in the substantia nigra pars compacta (>70%), but 3NP-induced discrete lesioned areas and cell loss predominantly in the putamen appeared only in the dystonic and levodopa-unresponsive animal. We propose that the appearance of dystonia after 3NP intoxication following dopaminergic striatal denervation is the key symptom predictive of the loss of dopaminergic response.
authors.affiliation: CNRS-UMR 5543, Université Victor Segalen Bordeaux 2, 146, rue Léo-Saignat, 33076 Bordeaux Cedex, France.
authors.forename: I
authors.initials: I
authors.lastname: Ghorayeb
authors.forename: P O
authors.initials: PO
authors.lastname: Fernagut
authors.forename: N
authors.initials: N
authors.lastname: Stefanova
authors.forename: G K
authors.initials: GK
authors.lastname: Wenning
authors.forename: B
authors.initials: B
authors.lastname: Bioulac
authors.forename: F
authors.initials: F
authors.lastname: Tison
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents; D004421:Dystonia / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D007980:Levodopa / Q000627:therapeutic use; D008252:Macaca fascicularis; D009498:Neurotoxins; D009574:Nitro Compounds; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D011422:Propionates; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D020955:Striatonigral Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D015259:Dopamine Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C015392:3-nitropropionic acid; D004298:Dopamine