Neurochemical and behavioral effects of systematic and intranigral administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the rat

Chiueh, Chuang C.; Markey, Sanford P.; Burns, R. S.; Johannessen, Jan N.; Pert, Agu; Kopin, Irwin J.

doi:10.1016/0014-2999(84)90221-8

Cited by 214 publications

(45 citation statements)

References 8 publications

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“…Effects in the striatum were maximal after 2 h and lasted for more than 6 h.'l The accumulation of 3,4-dihydroxyphenylalanine (DOPA) after inhibition of aroma tic amino acid decarboxylase by NSD-1015 was reduced by MPTP, indicating a reduced synthesis of dopamine in vivo.21 Pretreatment or' rats with dopamine and norepinephrine uptake blockers (nomifensine and desipramine) failed to effect MPTP-induced r,eduction in striatal DOPAC. 21 In the nerve terminal region of the nigrostriatal system, the caudate nucleus, dopamine content was increased 2 h after a single 10 mgkg dose, whereas levels in the nucleus accumbens were unchanged.z A single injection of MPTP accelerated metabolism of cortical norepinephrine as indicated by a decrease in norepinephrine levels and an increase in the levels of its metabolite MHPG. 21 In the mouse, MPTP produces dose-dependent reductions of dopamine in the striatum and norepinephrine in the frontal cortex, with maximal effects seen 1 h after i.v.…”

Section: Dogmentioning

confidence: 98%

The pharmacology of the parkinsonian syndrome producing neurotoxin MPTP (1–methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) and structurally related compounds

Markey

Schmuff²

1986

Medicinal Research Reviews

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Section: Dogmentioning

confidence: 98%

The pharmacology of the parkinsonian syndrome producing neurotoxin MPTP (1–methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) and structurally related compounds

Markey

Schmuff²

1986

Medicinal Research Reviews

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“…In most studies on rodents, rats have been shown to be resistant to systemic administration of MPTP (Boyce et al 1984;Chiueh et al 1984) while the effects in mice depend upon the strain studied (Sundstrom et al 1987;Sonsalla & Heikkila 1988). A number of MPTP analogues have also been described of which l-methyl-4-(2'-methylpheny1)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP) is more potent than MPTP (Youngster et al 1986) and mainly oxidized by MAO-A (Sonsalla et ul.…”

mentioning

confidence: 99%

Comparison of Key Steps in 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) Neurotoxicity in Rodents

Sundström

Samuelsson

1997

Pharmacology & Toxicology

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Three steps in I-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) neurotoxicity were compared with the neurodegenerative effects of the toxin in mice and rats. Firstly, we compared the neurotoxicity of MPTP, mediated by monoamine oxidase (MA0)-B, to that of I-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP). an analogue oxidized by MAO-A and MAO-B. Both toxins caused degeneration of dopamine terminals in mice but not in rats. In NMRI mice noradrenaline terminals were also affected by both toxins. Pretreatment with deprenyl to prevent MAO-B-mediated oxidation in the capillary endothelium enhanced dopamine toxicity to 2'-CH3-MFTP in nucleus accumbens but no potentiation was seen in striatum and the olfactory tubercle. Secondly, synaptosomal uptake of the I-methyl-4-phenylpyridinium ion (MPP+) was studied. Uptake in rats was not significantly different from that in the two mice strains. Thirdly, no significant differences were found in MPP+-induced lactate production in striatal slices or synaptosomes. We conclude that the lack of effect of MPTP in rats is not due to mechanisms specific for MPTP but probably to the ability of rat catecholamine neurons to cope with, and survive, impaired energy metabolism.

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“…MPTP is used mainly in nonhuman primates and mice but has also been used in many other species such as dogs and cats [45]. For unknown reasons, rats are resistant to MPTP and mouse strains vary widely in their sensitivity to the toxin [46]. MPTP can be administered by a variety of regimens, but the most common and reproducible form is still systemic injection (subcutaneous, intravenous) [47].…”

Section: Mptpmentioning

confidence: 99%

The Effect of Treadmill Exercise on Expression of α-synuclein and miRNA in MPTP Induced-mouse Models of Parkinson’s Disease

Moon¹,

Choi²,

Oh³

et al. 2017

Exerc Sci

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Neurological disorders can be modeled in animals so as to recreate specific pathogenic events and behavioral outcomes. Parkinson's Disease (PD) is the second most common neurodegenerative disease of an aging population, and although there have been several significant findings about the PD disease process, much of this process still remains a mystery. Breakthroughs in the last two decades using animal models have offered insights into the understanding of the PD disease process, its etiology, pathology, and molecular mechanisms. Furthermore, while cellular models have helped to identify specific events, animal models, both toxic and genetic, have replicated almost all of the hallmarks of PD and are useful for testing new neuroprotective or neurorestorative strategies. Moreover, significant advances in the modeling of additional PD features have come to light in both classic and newer models. In this review, we try to provide an updated summary of the main characteristics of these models as well as the strengths and weaknesses of what we believe to be the most popular PD animal models. These models include those produced by 6-hydroxydopamine (6-OHDA), 1-methyl-1,2,3,6-tetrahydropiridine (MPTP), rotenone, and paraquat, as well as several genetic models like those related to alpha-synuclein, PINK1, Parkin and LRRK2 alterations.

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Neurochemical and behavioral effects of systematic and intranigral administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the rat

Cited by 214 publications

References 8 publications

The pharmacology of the parkinsonian syndrome producing neurotoxin MPTP (1–methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) and structurally related compounds

The pharmacology of the parkinsonian syndrome producing neurotoxin MPTP (1–methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) and structurally related compounds

Comparison of Key Steps in 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) Neurotoxicity in Rodents

The Effect of Treadmill Exercise on Expression of α-synuclein and miRNA in MPTP Induced-mouse Models of Parkinson’s Disease

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