A beam-walking apparatus to assess behavioural impairments in MPTP-treated mice: pharmacological validation with R-(-)-deprenyl.
A beam-walking apparatus has been evaluated for its ability to detect motor impairments in mice acutely treated with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg, s.c., single or double administration). Mice subjected to MPTP lesioning showed deficits in motor performance on the beam-walking task, for up to 6 days post-MPTP administration, as compared to saline-treated controls. In addition, MPTP-treated mice were detected to have a marked depletion in striatal dopamine levels and a concomitant reduction in substantia nigra (SN) tyrosine hydroxylase (TH) immunoreactivity, at 7 days post-MPTP administration, indicative of dopaminergic neuronal loss. Pre-administration of the potent MAO-B inhibitor R-(-)-deprenyl at 3 or 10 mg/kg, 30 min, s.c, significantly inhibited the MPTP-induced reduction in SN TH-immunoreactivity, striatal dopamine depletions and impairments in mouse motor function. The data described in the present study provides further evidence that functional deficits following an acute MPTP dosing schedule in mice can be quantified and are related to nigro-striatal dopamine function.
Quinn
Leann P
LP
Neurology & GI CEDD, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. leann.p.quinn@gsk.com
Perren
Marion J
MJ
Brackenborough
Kim T
KT
Woodhams
Peter L
PL
Vidgeon-Hart
Martin
M
Chapman
Helen
H
Pangalos
Menelas N
MN
Upton
Neil
N
Virley
David J
DJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004298:Dopamine / Q000172:deficiency*; D004305:Dose-Response Relationship, Drug; D005010:Ethology / Q000295:instrumentation* / Q000379:methods; D020233:Gait Disorders, Neurologic / Q000175:diagnosis* / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009480:Neuropharmacology / Q000295:instrumentation* / Q000379:methods; D020734:Parkinsonian Disorders / Q000175:diagnosis* / Q000503:physiopathology / Q000517:prevention & control; D011237:Predictive Value of Tests; D012642:Selegiline / Q000627:therapeutic use; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine