Effects of MPTP on locomotor activity in mice

Colotla, Víctor A.; Flores, Eduardo; Oscos, Alejandro; Meneses, Alfredo; Tapia, Ricardo

doi:10.1016/0892-0362(90)90061-g

Cited by 54 publications

(24 citation statements)

References 7 publications

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“…In agreement with previous studies (Miyoshi et al, 2002;Da Cunha et al, 2001, 2003Gevaerd et al, 2001a,b), the bilaterally MPTP-lesioned rats presented relatively few motor alterations, a finding that can be explained by their reduced dopamine cell loss and striatal dopamine depletion, with this entire picture being suitable to study the cognitive impairment that occurs in the motor presymptomatic phase of PD. Indeed, MPTP-lesioned rats and mice (Kordower et al, 1986;Colotla et al, 1990;Chia et al, 1996) showed increased locomotor activity. Other authors reported decreased locomotor activity (Sedelis et al, 2001).…”

Section: Discussionmentioning

confidence: 96%

Comparison of bilaterally 6-OHDA- and MPTP-lesioned rats as models of the early phase of Parkinson's disease: Histological, neurochemical, motor and memory alterations

Ferro

Bellissimo

Anselmo-Franci

et al. 2005

Journal of Neuroscience Methods

188

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Section: Discussionmentioning

confidence: 96%

Comparison of bilaterally 6-OHDA- and MPTP-lesioned rats as models of the early phase of Parkinson's disease: Histological, neurochemical, motor and memory alterations

Ferro

Bellissimo

Anselmo-Franci

et al. 2005

Journal of Neuroscience Methods

188

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“…Several studies have described motor function disturbances in MPTP-treated mice to relate the deficits to symptoms in humans with PD. Motor function tests in MPTP-treated mice have included grip strength [40], the ability of the animals to balance on a rotating rod [27,40], and swimming performance [51]. MPTP significantly affects locomotor activity [17,40,52] and motor performance [17,20,28,51], thus providing functional readouts to test potential therapies.…”

Section: Discussionmentioning

confidence: 99%

“…to 7 mice every 24 hours for 3 days (MPTP-treated mice), based on previously published studies [40,41]. Equivolume (0.2 ml) of saline was administered i.p.…”

Section: Methodsmentioning

confidence: 99%

Gait dynamics in mouse models of Parkinson's disease and Huntington's disease

Amende

Kale

McCue

et al. 2005

J NeuroEngineering Rehabil

149

103

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BackgroundGait is impaired in patients with Parkinson's disease (PD) and Huntington's disease (HD), but gait dynamics in mouse models of PD and HD have not been described. Here we quantified temporal and spatial indices of gait dynamics in a mouse model of PD and a mouse model of HD.MethodsGait indices were obtained in C57BL/6J mice treated with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg/day for 3 days) for PD, the mitochondrial toxin 3-nitropropionic acid (3NP, 75 mg/kg cumulative dose) for HD, or saline. We applied ventral plane videography to generate digital paw prints from which indices of gait and gait variability were determined. Mice walked on a transparent treadmill belt at a speed of 34 cm/s after treatments.ResultsStride length was significantly shorter in MPTP-treated mice (6.6 ± 0.1 cm vs. 7.1 ± 0.1 cm, P < 0.05) and stride frequency was significantly increased (5.4 ± 0.1 Hz vs. 5.0 ± 0.1 Hz, P < 0.05) after 3 administrations of MPTP, compared to saline-treated mice. The inability of some mice treated with 3NP to exhibit coordinated gait was due to hind limb failure while forelimb gait dynamics remained intact. Stride-to-stride variability was significantly increased in MPTP-treated and 3NP-treated mice compared to saline-treated mice. To determine if gait disturbances due to MPTP and 3NP, drugs affecting the basal ganglia, were comparable to gait disturbances associated with motor neuron diseases, we also studied gait dynamics in a mouse model of amyotrophic lateral sclerosis (ALS). Gait variability was not increased in the SOD1 G93A transgenic model of ALS compared to wild-type control mice.ConclusionThe distinct characteristics of gait and gait variability in the MPTP model of Parkinson's disease and the 3NP model of Huntington's disease may reflect impairment of specific neural pathways involved.

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“…For example, when administered peripherally to primates (Kupsch et al, 1996;Melaga et aI., 1996) or mice Fredriksson and Archer, 1994), MPTP decreases striatal DA levels and leads to a loss of DA cells in the ventral mesencephalon, especially the substantia nigra. Behaviorally, such systemic MPTP treatments can affect performance in a number of tests, including open field (Frederiksson and Archer, 1994), rotarod (Rozas et al, 1998), grip test (Colotla et al, 1990), pole test (Ogawa et aI., 1985), swim test (Donnan et aI., 1987), measures of tremor (Lee and Lu, 1995), and tests for akinesia and somatosensory orientation (Weihmuller et al, 1990). Despite having sustained substantial striatal DA denervations such mice can recover remarkably from initial deficits, which is similar to what is seen in other dopaminergic lesion models, like the 6-OHDA model in the rat (for review see Schwarting and Huston, 1996a,b;Zigmond et aI., 1990).…”

Section: Introductionmentioning

confidence: 99%

Strain-dependent recovery of open-field behavior and striatal dopamine deficiency in the mouse MPTP model of Parkinson’s disease

et al. 1999

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The neurotoxin MPTP can damage dopamine systems in the brains of rodents, cats, or monkeys, and is therefore widely used to model degenerative processes that underlie human Parkinson's disease. Here, we investigated the relationships between behavioral and neurochemical effects of systemic MPTP treatment in C57Bl/6 and Balb/c mice. Initially, different doses of MPTP were used to determine which of them might be useful to establish severe striatal dopamine depletions. These data showed that four injections of 20mg/kg at two hour intervals, were more efficient than 10 or 15mg/kg per injection. However, this dose was not usable due to its severe lethality in females. In contrast, 4x 15mg/kg had a low risk of lethality and led to substantial dopamine depletions, which were more severe in the neostriatum than the ventral striatum, and more severe in C57 than in Balb mice. In the first open field test, which was performed two hours after the last injection, this treatment led to severe behavioral inactivation in all parameters taken (distance and speed of locomotion, peripheral activity, frequency and duration of rearing). This effect was seen in both strains and gender. Thereafter, recovery differed between strains, since Balb mice, which had sustained the smaller lesions, had completely recovered on the subsequent day, whereas similar recovery took longer in C57 mice. On the fourth day, all groups appeared largely normal; however, the measure of rearing behavior still showed a deficit in C57 mice. This deficit on day 4 was correlated with neostriatal dopamine depletion; that is, the larger the lesion, the less the number and duration of rearings. Interestingly, these relationships were also observed with respect to ventral striatal dopamine damage, which was correlated with the rearing deficit not only on day 4, but also on day 1. These data will be discussed with respect to mechanisms of toxicity, functional recovery, and the function of striatal dopamine systems.

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Effects of MPTP on locomotor activity in mice

Cited by 54 publications

References 7 publications

Comparison of bilaterally 6-OHDA- and MPTP-lesioned rats as models of the early phase of Parkinson's disease: Histological, neurochemical, motor and memory alterations

Comparison of bilaterally 6-OHDA- and MPTP-lesioned rats as models of the early phase of Parkinson's disease: Histological, neurochemical, motor and memory alterations

Gait dynamics in mouse models of Parkinson's disease and Huntington's disease

Strain-dependent recovery of open-field behavior and striatal dopamine deficiency in the mouse MPTP model of Parkinson’s disease

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