Neural mechanisms underlying motor dysfunction as detected by the tail suspension test in MPTP-treated C57BL/6 mice.
Contradictory data on behavioral changes in MPTP-treated C57BL/6 mice have been reported, even though the toxin-treated mice have been widely used for non-clinical studies as an in vivo model of Parkinson's disease (PD). We found that the duration of immobility in the tail suspension test (TST) was significantly increased in MPTP-treated C57BL/6 mice as compared with control mice without a significant change in the locomotor activity (LA). Dopamine (DA) contents and protein levels of tyrosine hydroxylase and dopamine transporter in the striatum were profoundly decreased in the toxin-treated mice. These behavioral and neurobiochemical changes were almost completely inhibited by a pretreatment with deprenyl, a monoamine oxidase-B inhibitor. The stimulation of dopaminergic neurotransmission induced by L-dopa or a dopamine D2 receptor agonist ameliorated the increase in immobility time. Threshold level of striatal DA that produced the increase in immobility time in MPTP-treated mice was estimated to be between 11 and 27% of control level. We concluded that the increase in immobility time in the TST was induced by the nigrostriatal dopaminergic degeneration and was thought to be a consequence of motor dysfunction in this mouse model of PD.
Mori
Atsushi
A
Research Unit for Neurological Diseases, Second Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Tokushima-city, Tokushima 771-0192, Japan.
Ohashi
Satoshi
S
Nakai
Masami
M
Moriizumi
Tetsuji
T
Mitsumoto
Yasuhide
Y
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D001923:Brain Chemistry / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019417:Hindlimb Suspension / Q000379:methods*; D046353:Immobility Response, Tonic / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008996:Monoamine Oxidase Inhibitors; D009419:Nerve Tissue Proteins; D012642:Selegiline; D001971:Bromocriptine; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine