Treatment with a selective MAO B inhibitor prevents loss of dopamine in the nucleus accumbens of MPTP-treated common marmosets.
Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets induced motor deficits, associated with a marked decrease in the uptake of [3H]dopamine into synaptosomes in the putamen and a reduction in the content of dopamine in both caudate nucleus and nucleus accumbens. Histological analysis showed a marked loss of dopamine-containing cells in the zona compacta of the substantia nigra and less loss in the ventral tegmental area. Treatment of animals with the selective monoamine oxidase (MAO) B inhibitor, MDL 72145 (0.5 or 2.0 mg/kg) prior to, during and following administration of MPTP partially protected animals from the motor abnormalities induced by administration of MPTP alone. Both doses inhibited the onset of akinesia but only the large dose of MDL 72145 prevented the occurrence of other motor abnormalities. Moreover, while MDL 72145 (2.0 mg/kg) prevented the loss in uptake of [3H]dopamine into synaptosomes of the putamen, this was only partly prevented using the smaller dose. Similarly, while MDL 72145 (2.0 mg/kg) prevented loss of dopamine in the caudate, only partial protection was afforded by the smaller dose. However, in the nucleus accumbens, both doses of MDL 72145 prevented the depletion of dopamine, occurring in this region. Histological examination of the substantia nigra showed little or no cell loss in animals receiving the larger dose of MDL 72145 but a moderate cell loss in animals receiving the smaller dose. No damage was observed in the ventral tegmental area of animals treated with MDL 72145 (2.0 mg/kg) and only mild cell loss in those receiving the smaller dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Rose
S
S
Parkinson's Disease Society Research Centre, University Department of Neurology, London, U.K.
Nomoto
M
M
Jackson
E A
EA
Gibb
W R
WR
Jenner
P
P
Marsden
C D
CD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000499:Allylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001679:Biogenic Amines / Q000378:metabolism; D002143:Callitrichinae; D002421:Caudate Nucleus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D011699:Putamen / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D012686:Septal Nuclei / Q000378:metabolism*
D001679:Biogenic Amines; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D000499:Allylamine; C040051:2-(3,4-dimethoxyphenyl)-3-fluoroallylamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid