Chronic neurochemical and behavioral changes in MPTP-lesioned C57BL/6 mice: a model for Parkinson's disease.
The long-term effect of the parkinsonism inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on pre- and postsynaptic structures of the nigrostriatal and mesolimbic dopamine (DA) system in adult C57BL/6 mice (2 x 40 mg/kg s.c.) was investigated using neurochemical and behavioral methods. It was found that MPTP induced a severe depletion of striatal DA levels (-80%) that persists for 4 weeks after treatment, with less severe effects in nucleus accumbens (-36%) and the olfactory tubercle (-52%). These depletions are associated with decreased tyrosine hydroxylase (TH) activity as determined in vivo and increased turnover of DA. MPTP treatment did not induce any change in the DA2-receptor as determined by [3H]spiperone binding or by two different behavioral tests, i.e. apomorphine-induced climbing and apomorphine-induced stereotypies. No significant weight loss during 4 weeks after MPTP was found. The spontaneous motor activity in these mice was profoundly and persistently depressed (-66%) as a result of the MPTP-induced DA denervation and the motor deficit was completely reversed by L-DOPA treatment. We suggest that MPTP-treated C57BL/6 mice may serve as a suitable model for Parkinson's disease.
Sundström
E
E
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Fredriksson
A
A
Archer
T
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis; D006834:Hydrazines; D007980:Levodopa / Q000378:metabolism; D008297:Male; D008781:Methyltyrosines; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000378:metabolism / Q000523:psychology; D011954:Receptors, Dopamine / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects
D006834:Hydrazines; D008781:Methyltyrosines; D011954:Receptors, Dopamine; C022260:alpha-methyltyrosine methyl ester; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C004297:3-hydroxybenzylhydrazine; D001058:Apomorphine; D004298:Dopamine