Drug-free evaluation of rat models of parkinsonism and nigral grafts using a new automated rotarod test

Abstract

A variety of tests are available for the evaluation of behavioural deficits in rat models of hemiparkinsonism; many, however, are of limited applicability or insufficiently objective. The drug-induced turning behaviour test is widely used. A disadvantage of this test is that the use of drugs may lead to misleading results. Here, we describe a drug-free rotarod test that was used to evaluate the effects of unilateral 6-hydroxydopamine lesions, nigral grafts, and subrotational doses of apomorphine. The rotarod unit was automated and interfaced to a personal computer allowing automatic recording of the time that each rat was able to stay on the rod at different rotational speeds (i.e., progressively increasing the difficulty of the task). A combination of lesion-induced deficits resembling those of Parkinson's disease appears to be involved in falling from the rod. The test shows high effectiveness for identifying rats with maximal dopaminergic lesions, but is also effective for identifying partial lesions. Rotarod performance profiles were useful for investigating the effects of intrastriatal nigral grafts, since low rotation speeds revealed differences from lesioned rats (i.e., improvements) while higher speeds revealed differences from normal rats (i.e., remaining deficits and partial lesions). The test was effective regardless of whether rats were trained on the rod before lesion, after lesion, or after grafting. Injections of apomorphine (0.0125 and 0.0250 mg/kg) did not induce consistent improvements. These results indicate that the rotarod test is a useful drug-free procedure for overall evaluation of basic motor abilities in rat models of parkinsonism and treatment-induced changes.