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.
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.
Ghorayeb
I
I
CNRS-UMR 5543, Université Victor Segalen Bordeaux 2, 146, rue Léo-Saignat, 33076 Bordeaux Cedex, France.
Fernagut
P O
PO
Stefanova
N
N
Wenning
G K
GK
Bioulac
B
B
Tison
F
F
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
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