Behavioral phenotyping of the MPTP mouse model of Parkinson's disease

In mice, the systemical or intracranial application of the neurotoxin 1-met hyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can lead to severe damage to the nigrostriatal dopaminergic system. This can result in a variety of sym ptoms concerning motor control resembling those in human Parkinson's diseas e, such as akinesia. rigidity, tremor, gait and posture disturbances. The a im of this work is to review a variety of behavioral paradigms for these an d other symptoms. which have been used to characterize behavioral changes i n mice after MPTP treatment. Main results are summarized. and general influ ential factors as well as potential problems in the experimental procedures are discussed, which should be taken into account when conducting behavior al analyses in mice with parkinsonian symptoms. Since there is reliable evi dence (e.g. from strain comparisons) that the susceptibility of the nigrost riatal pathway to neurodegeneration is probably genetically influenced, rel evant genes can be expected to be identified in the future. Therefore, the points discussed here will be useful not only for further applications in t he MPTP mouse model, but also more generally for the behavioral characteriz ation of future mouse models of PD. e.g. mice with a manipulation of genes relevant to the function of the basal ganglia. (C) 2001 Elsevier Science B. V. All rights reserved.