Stanley, J.L. et al. The mouse beam walking assay offers improved sensitivity over the mouse rotarod in determining motor coordination deficits induced by benzodiazepines. J. Psychopharmacol. 19, 221-227

Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Harlow, UK.
Journal of Psychopharmacology (Impact Factor: 3.59). 06/2005; 19(3):221-7. DOI: 10.1177/0269881105051524
Source: PubMed


The mouse rotarod test of motor coordination/sedation is commonly used to predict clinical sedation caused by novel drugs. However, past experience suggests that it lacks the desired degree of sensitivity to be predictive of effects in humans. For example, the benzodiazepine, bretazenil, showed little impairment of mouse rotarod performance, but marked sedation in humans. The aim of the present study was to assess whether the mouse beam walking assay demonstrates: (i) an increased sensitivity over the rotarod and (ii) an increased ability to predict clinically sedative doses of benzodiazepines. The study compared the effects of the full benzodiazepine agonists, diazepam and lorazepam, and the partial agonist, bretazenil, on the mouse rotarod and beam walking assays. Diazepam and lorazepam significantly impaired rotarod performance, although relatively high GABA-A receptor occupancy was required (72% and 93%, respectively), whereas beam walking performance was significantly affected at approximately 30% receptor occupancy. Bretazenil produced significant deficits at 90% and 53% receptor occupancy on the rotarod and beam walking assays, respectively. The results suggest that the mouse beam walking assay is a more sensitive tool for determining benzodiazepine-induced motor coordination deficits than the rotarod. Furthermore, the GABA-A receptor occupancy values at which significant deficits were determined in the beam walking assay are comparable with those observed in clinical positron emission tomography studies using sedative doses of benzodiazepines. These data suggest that the beam walking assay may be able to more accurately predict the clinically sedative doses of novel benzodiazepine-like drugs.

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    • "Because of the vast range of situations in which such trade-offs are likely to constrain performance, we wanted to develop a model that could easily be modified to suit different systems or scenarios. Obviously, the model applies to studies of animals walking or running on beams (Losos and Sinervo 1989; Goldstein and Davis 1990; Llewellyn et al. 1990; Sinervo and Losos 1991; Losos and Irschick 1996; Speers et al. 1998; Buddeberg et al. 2004; Stanley et al. 2005; Vanhooydonck et al. 2006), but the model is not limited to these situations. Width of the beam can be set as constant for studies that do not vary the width of the substrate; similarly, the runway need not be a beam. "
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    ABSTRACT: How fast should animals move when trying to survive? Although many studies have examined how fast animals can move, the fastest speed is not always best. For example, an individual escaping from a predator must run fast enough to escape, but not so fast that it slips and falls. To explore this idea, we developed a simple mathematical model that predicts the optimal speed for an individual running from a predator along a straight beam. A beam was used as a proxy for straight-line running with severe consequences for missteps. We assumed that success, defined as reaching the end of the beam, had two broad requirements: (1) running fast enough to escape a predator, and (2) minimizing the probability of making a mistake that would compromise speed. Our model can be tailored to different systems by revising the predator's maximal speed, the prey's stride length and motor coordination, and the dimensions of the beam. Our model predicts that animals should run slower when the beam is narrower or when coordination is worse. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email:
    Integrative and Comparative Biology 08/2015; DOI:10.1093/icb/icv091 · 2.93 Impact Factor
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    • "However, constant testing environments such as testing within the animal's cage are necessary in order to retrieve reliable and valid data in the adhesive removal test (Schallert and Woodlee, 2005), as should be the case for any other behavioral test as well. Similar findings were found regarding the balance beam test, which was more sensitive in assessment of motor coordination deficits than the rota rod test, albeit these tests were performed in a non-stroke model (Stanley et al., 2005). On the contrary, the pole test cannot be recommended for conditions of severe stroke since some animals are not able to perform the test at all due to the strenuous nature of the task, as has been discussed afore regarding the tight rope test. "
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    ABSTRACT: Systemic transplantation of neural progenitor cells (NPCs) in rodents reduces functional impairment after cerebral ischemia. In light of upcoming stroke trials regarding safety and feasibility of NPC transplantation, experimental studies have to successfully analyze the extent of NPC-induced neurorestoration on the functional level. However, appropriate behavioral tests for analysis of post-stroke motor coordination deficits and cognitive impairment after NPC grafting are not fully established. We therefore exposed male C57BL6 mice to either 45 min (mild) or 90 min (severe) of cerebral ischemia, using the thread occlusion model followed by intravenous injection of PBS or NPCs 6 h post-stroke with an observation period of three months. Post-stroke motor coordination was assessed by means of the rota rod, tight rope, corner turn, inclined plane, grip strength, foot fault, adhesive removal, pole test and balance beam test, whereas cognitive impairment was analyzed using the water maze, the open field and the passive avoidance test. Significant motor coordination differences after both mild and severe cerebral ischemia in favor of NPC-treated mice were observed for each motor coordination test except for the inclined plane and the grip strength test, which only showed significant differences after severe cerebral ischemia. Cognitive impairment after mild cerebral ischemia was successfully assessed using the water maze test, the open field and the passive avoidance test. On the contrary, the water maze test was not suitable in the severe cerebral ischemia paradigm, as it too much depends on motor coordination capabilities of test mice. In terms of both reliability and cost-effectiveness considerations, we thus recommend the corner turn, foot fault, balance beam, and open field test, which do not depend on durations of cerebral ischemia.
    Frontiers in Cellular Neuroscience 10/2014; 8:338. DOI:10.3389/fncel.2014.00338 · 4.29 Impact Factor
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    • "The method previously described by Stanley et al. (2005) was used for this study with modifications. Briefly, each mouse was trained to walk from a start platform along a ruler (80 cm long, 3 cm wide) elevated 30 cm above the bench by metal support to a goal box (enclosed hamster house). "
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    ABSTRACT: Decoctions of Ficus platyphylla Del.-Holl (Family: Moraceae) are used in the Nigeria's folk medicine for the management of epilepsy and their efficacies are widely acclaimed among the rural communities of northern Nigeria. To examine the behavioral and anticonvulsant properties of the standardized methanol extract of Ficus platyphylla (FP) stem bark, in order to scientifically describe its potential values in the management of convulsive disorders. The High performance liquid chromatography (HPLC) and preliminary phytochemical analysis of the methanol extract were evaluated and the intraperitoneal median lethal dose (LD50) determined in mice. Effects of FP were investigated on some murine models of behavior and its anticonvulsant effects studied on pentylenetetrazole (PTZ)-, strychnine (STN)-, picrotoxin (PCT)-, isoniazid (INH)-, aminophylline (AMI) and maximal electroshock (MES) seizures in mice. The intraperitoneal oral LD50 of FP was estimated to be 5000mg/kg. FP significantly reduced the locomotor activities including the total distance covered, speed, active time and rearing counts. It shortened the onset and prolonged the duration of diazepam induced sleep, but had no effect on motor coordination on the rota-rod treadmill or beam-walking assay in mice at the doses tested. The extract protected the mice against PTZ and STN-induced seizures and significantly delayed the latencies of myoclonic jerks and tonic seizures induced by all the standard convulsant agents (PTZ, PCT, INH, STN and AMI) used in this study, but failed to protect the mice against MES seizures at doses tested. The HPLC fingerprint of the extract shows a spectrum profile characteristic of Ficus platyphylla, while the preliminary phytochemical screening revealed the presence of saponins, flavonoids and tannins. Our study provides scientific evidence that FP may contain psychoactive principles with potential anticonvulsant properties, thus supporting further development of the psychoactive components of this plant as anticonvulsant agents.
    Journal of ethnopharmacology 04/2014; 154(2). DOI:10.1016/j.jep.2014.03.061 · 3.00 Impact Factor
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