Acute electrophysiological and neurochemical effects of administration of MPTP in mice.
The changes occurring during the first few hours after subcutaneous administration of the catecholaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were investigated. Injections of MPTP (30-60 mg/kg s.c.) reduced the impulse rate by 12-45% in all dopaminergic neurones tested in the pars compacta of the substantia nigra. Depressions were maximal at 11 min and remained present for more than 2 hr after injection. This effect was completely abolished by prior administration of the catecholamine uptake inhibitor, nomifensine (13-69 mg/kg s.c.), which prevents the toxic metabolite of MPTP 1-methyl-4-phenylpyridine (MPP+) from entering dopaminergic neurones. These results suggest an intraneuronal mechanism underlying the observed depressions in impulse rate. Levels of dopamine (DA) were decreased at 3 hr after administration of MPTP (50 mg/kg s.c.) by 60% and 54% in the striatum and substantia nigra, respectively. Pretreatment with nomifensine (25 mg/kg, intraperitoneally) prevented the decrease in DA only in the striatum. This suggests an acute DA-releasing effect of MPTP in the striatum, mediated by intracellular accumulation of MPP+, while not explaining the depression of activity of DA neurones occurring with a different time course.
Studer
A
A
Institut de Physiologie, Université de Fribourg, Switzerland.
Sundström
E
E
Jonsson
G
G
Schultz
W
W
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D009627:Nomifensine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects
D011725:Pyridines; D009627:Nomifensine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine