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Electrophysiological and neurochemical correlates of the neurotoxic effects of 1 methyl 4 phenyl 1 2 3 6 tetrahydropyridine on central catecholamine neurons in the mouse


, : Electrophysiological and neurochemical correlates of the neurotoxic effects of 1 methyl 4 phenyl 1 2 3 6 tetrahydropyridine on central catecholamine neurons in the mouse. Naunyn-Schmiedeberg's Archives of Pharmacology 331(1): 1-6

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an agent which produces a parkinsonian syndrome in man. To explore the use of MPTP in a rodent model of parkinsonism, male albino mice (NMRI) were given MPTP (50 mg/kg, s.c.) twice with a 6-8 h interval. Up to 10 weeks after injection, mice were killed and high-pressure liquid chromatography was used to assay dopamine (DA) and noradrenaline (NA) concentrations in various regions of the CNS. At 4 and 10 weeks after injection, DA levels were significantly reduced in occipital cortex (-40%), hippocampus (-30%), and striatum (-60%). NA levels were reduced by 60-80% in frontal and occipital cortex, hippocampus, and cerebellum. Neither DA nor NA concentration was reduced in spinal cord. Dopaminergic denervation was also suggested by electrophysiological data which showed that treatment with MPTP increased the spontaneous discharge rate of caudate neurons and decreased the potency of locally administered phencyclidine, an indirect DNA agonist. However, denervation was evidently not complete enough to produce postsynaptic receptor supersensitivity, as MPTP treatment did not increase the potency of locally applied DA, and it did not increase 3H-spiperone binding in striatal membrane preparations. These results suggest that MPTP causes regionally selective and long-term reductions of catecholamine transmission in the CNS of the mouse.

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Related references

Jonsson, G.; Sundström, E.; Mefford, I.; Olson, L.; Johnson, S.; Freedman, R.; Hoffer, B., 1985: Electrophysiological and neurochemical correlates of the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in the mouse. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an agent which produces a parkinsonian syndrome in man. To explore the use of MPTP in a rodent model of parkinsonism, male albino mice (NMRI) were given MPTP (50 mg/kg, s.c.) twice with a 6-8...

Hallman H.; Lange J.; Olson L.; Stromberg I.; Jonsson G., 1985: Neurochemical and histochemical characterization of neurotoxic effects of 1 methyl 4 phenyl 1 2 3 6 tetrahydropyridine on brain catecholamine neurons in the mouse. Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP[which causes chronic parkinsonism]) caused a rapid and long-lasting reduction of both 3,4-dihydroxyphenylalanine (dopamine, DA) and noradrenaline[norepinephrine] (NA) in...

Hallman, H.; Lange, J.; Olson, L.; Strömberg, I.; Jonsson, G., 1985: Neurochemical and histochemical characterization of neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain catecholamine neurones in the mouse. Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused a rapid and long-lasting reduction of both 3,4-dihydroxyphenylalanine (dopamine, DA) and noradrenaline (NA) in mouse brain, as observed histo- and neurochemicall...

Sundstrom E.; Jonsson G., 1985: Pharmacological interference with the neurotoxic action of 1 methyl 4 phenyl 1 2 3 6 tetrahydropyridine on central catecholamine neurons in the mouse. The effect of pretreatment with various MAO [monoamine oxidase] and catecholamine uptake inhibitors on the MPTP[1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine]-induced reduction of endogenous catecholamine levels and [3H]catecholamine uptake in mous...

Sundstrom E.; Hallman H.; Olson L.; Stromberg I.; Jonsson G., 1984: Neurotoxic effects of n methyl 4 phenyl 1 2 3 6 tetrahydropyridine on brain catecholamine neurons in the mouse. Neuroscience Letters (SUPPL 18): S202

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Sundstrom E.; Jonsson G., 1985: Monoamine oxidase and catecholamine uptake inhibition protect catecholamine neurons in mouse brain from the neurotoxic actions of 1 methyl 4 phenyl 1 2 3 6 tetrahydropyridine. Journal of Neurochemistry 44(SUPPL): S183

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