Animal models of neurological deficits: how relevant is the rat?

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Animal models of neurological deficits are essential for the assessment of new therapeutic options. It has been suggested that rats are not as appropriate as primates for the symptomatic modelling of disease, but a large body of data argues against this view. Comparative analyses of movements in rats and primates show homology of many motor patterns across species. Advances have been made in identifying rat equivalents of akinesia, tremor, postural deficits and dyskinesia, which are relevant to Parkinson's disease. Rat models of hemiplegia, neglect and tactile extinction are useful in assessing the outcome of ischaemic or traumatic brain injury, and in monitoring the effects of therapeutic interventions. Studies in rodents that emphasize careful behavioural analysis should continue to be developed as effective and inexpensive models that complement studies in primates.

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We wish to thank M. Woodlee and P. Whishaw for their help, and P. Hagell, M.-L. Smith and P. Mohapel for critical discussions.

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Correspondence to M. Angela Cenci.

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Movie 1 | Skilled limb movements in an intact ratA control rat reaches for a food pellet using normal movements. A detailed analysis of its skilled limb movements reveals very similar motor components in humans and in rats. (MOV 772 kb)

Movie 2 | Tremor at restOccasional resting tremor has been observed in the wrist and the paw of rats that have been lesioned with 6-hydroxydopamine (6-OHDA). Tremor occurs when the forelimb is not being used for movement or postural support in the home cage. (MOV 196 kb)

Movie 3 | Akinesia in a rat model of Parkinson’s disease Severe unilateral loss of nigrostriatal dopamine terminals in a rat 1.6 years after the infusion of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle in the right hemisphere. The rat shows deficits in movement initiation (spontaneous stepping) with its left, but not its right, forelimb. In this test, the experimenter does not impose weight shifting; rather, the rat is allowed to initiate stepping on its own. Note that normal rats use primarily their forelimbs, rather than their hindlimbs, to initiate walking. (MOV 400 kb)

Movie 4 | The cylinder testThe cylinder test: Limb-use asymmetry caused by unilateral loss of nigrostriatal dopamine after infusion of 6-hydroxydopamine (6-OHDA) into the nigrostriatal projections of the left hemisphere. The rat shows a preference for the left forelimb when initiating weight-shifting movements during vertical/lateral exploration. Use of the right forelimb is impaired; it is not used independently for weight shifts, support or stepping movements on the walls of the cylinder. The level of dopamine-terminal loss is correlated with percentage preferential use of the non-impaired forelimb. (MOV 776 kb)

Movie 5 | Skilled limb movements in a 6-OHDA-lesioned ratRats with unilateral 6-hydroxydopamine (6-OHDA) lesions show abnormalities in both quantitative and qualitative aspects of reach-to-grasp movements on the side contralateral to dopamine depletion. When approaching a target, the impaired limb makes fragmented rather than concurrent movements, and shows incomplete pronation on the substrate. The deficits are partially compensated for using whole-body movements. (MOV 861 kb)

Movie 6 | Minimal dyskinesiaWhen treated with 3,4-dihydroxyphenylalanine (l-DOPA), rats with unilateral 6-hydroxydopamine (6-OHDA) lesions can show abnormal involuntary movements (AIMs), which mainly affect the forelimb contralateral to the lesion, the trunk and the orofacial musculature. These abnormal involuntary movements can be quantified on the basis of their topographical distribution, amplitude and duration; that is, using the same criteria that are used in the clinic. This sequence of movies shows rats with l-DOPA-induced AIMs of increasing amplitude and severity. (MOV 921 kb)

Movie 7 | Noticeable dyskinesia (MOV 951 kb)

Movie 8 | Moderate dyskinesia (MOV 966 kb)

Movie 9| Severe dyskinesia (MOV 1363 kb)

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Cenci, M., Whishaw, I. & Schallert, T. Animal models of neurological deficits: how relevant is the rat?. Nat Rev Neurosci 3, 574–579 (2002) doi:10.1038/nrn877

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