Behavioral Tests for Preclinical Intervention Assessment

Department of Psychology, Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712, USA.
NeuroRx 11/2006; 3(4):497-504. DOI: 10.1016/j.nurx.2006.08.001
Source: PubMed


Select functional outcome tests commonly used for evaluating sensorimotor and cognitive capacity in rodents with focal intracerebral ischemic or hemorrhagic injury are described, along with upgrades and issues of concern for translational research. An emphasis is placed on careful quantitative and qualitative assessment of acute and long-term behavioral deficits, and on avoidance of frequent pitfalls. Methods for detecting different degrees of injury and treatment-related improvements are included. Determining the true potential of an intervention requires a set of behavioral analyses that can monitor compensatory learning. In a number of preclinical outcome tests, animals can develop remarkably effective "tricks" that are difficult to detect but frequently lead to dramatic improvements in performance, particularly with repeated practice. However, some interventions may facilitate learning without promoting brain repair, but these may not translate into a meaningful level of benefit in the clinic. Additionally, it is important to determine whether there are any preinjury functional asymmetries in order to accurately assess damage-related changes in behavior. This is illustrated by the fact that some animals have chronic endogenous asymmetries and that others, albeit infrequently, can sustain a spontaneous cerebral stroke, without any experimental induction, that can lead to chronic deficits as reflected by behavioral, imaging, and histological analyses. Finally, a useful new modification of the water maze that involves moving the platform from trial to trial within the target quadrant is reviewed, and its advantages over the standard version are discussed.

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    • "The predictive validity is arguably one of the most important and is typically defined as the ability of a rodent behavioral test to predict the effect of a drug in humans. Determining the predictive validity requires an existing clinical treatment which can be back-tested in the rodent behavioral test under evaluation (Schallert, 2006). An example is benzodiazepines, which are widely used to treat anxiety in patients and also reduce the extent of rodents' anxiety-like behavior in both the light-dark box test (Crawley and Goodwin, 1980) and the EPM (Pellow and File, 1986). "
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    • "The measurement of the number of forelimb wall contacts produced scores that represent overall asymmetry, which is correlated closely with the degree of striatal DA depletion (Schallert and Tilleron, 2000; Cenci and Lundblad, 2005). The individual use of each forelimb was calculated according to Schallert (2006), and using the following calculation: % ipsilateral forelimb = [(ipsilateral + "
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    • "This test evaluates the spontaneous exploratory behavior of rodents [40], [41]. The cylinder test reveals forelimb preference when the animal rears to explore its environment by making forelimb contact with the cylinder walls. "
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