No apparent difference in the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the sympathetic system in NMRI and C57 BL/6 mice.
The parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to possess marked species as well as strain differences in toxicity on central catecholaminergic systems. In the present study the effects on the peripheral sympathetic nervous system following treatment with MPTP, as well as its metabolite 1-methyl-4-phenylpyridine (MPP+) and the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) were studied in mice of the NMRI and C57 BL/6 strains, two strains that possess marked difference in MPTP toxicity on central catecholaminergic neurons. No strain differences in the depletions of noradrenaline (NA) in iris and heart auricula and of NA and dopamine (DA) in superior cervical ganglion or in the reduction of the in vitro [3H]NA uptake in iris or heart auricula were found following MPTP treatment (2 X 40 mg/kg s.c., 2 and 7 days). Treatment with the NA uptake blocker desipramine (DMI) did not affect the MPTP-induced NA depletion in either strain. Following treatment with MPP+ (30 mg/kg i.v., 7 days) no differences in the two strains were seen on the reduction of NA levels in iris and heart auricula or decrease in [3H]NA uptake. In addition, no differences were found on NA levels in iris and heart auricula after 6-OHDA treatment (15 mg/kg i.v., 7 days). The data indicate that in the NMRI and C57 BL/6 mice peripheral NA neurons do not possess any notable strain difference in the vulnerability to MPTP or in the mechanism of action of MPTP.
Luthman
J
J
Department of Histology and Neurobiology, Karolinska Institute, Stockholm, Sweden.
Sundström
E
E
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D006321:Heart / Q000187:drug effects; D006892:Hydroxydopamines / Q000633:toxicity; D007279:Injections, Subcutaneous; D007498:Iris / Q000187:drug effects / Q000378:metabolism; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D013045:Species Specificity; D013564:Sympathetic Nervous System / Q000187:drug effects*
D006892:Hydroxydopamines; D016627:Oxidopamine; D015655:1-Methyl-4-phenylpyridinium; D009638:Norepinephrine