Early behavioral changes after nigro-striatal system damage can serve as predictors of striatal dopamine depletion

Abstract

1. Rats which had received a unilateral injection of 6-OHDA into the substantia nigra were assigned to four lesion groups according to the degree of DA depletion in the neostriatum. In these animals, behavioral changes in the open-field were investigated during the first post-operative week. Overall, this analysis showed that the animals could adequately be characterized by behavior on day 1 and day 7 after lesion. 2. On the first day after lesion, the groups with the severest DA depletions ( > 80% and 55–80%) showed an ipsilateral asymmetry in turning. After one week, these groups showed a tendency to recover from this deficit; however, the group with the most strongest lesions ( > 80%) was still asymmetric. 3. In scanning behavior, in contrast to turning, all the lesion groups displayed an initial ipsilateral asymmetry. On day 7 after lesion, only the group with DA depletions of > 80% still had an ipsilateral asymmetry. Locomotor activity and rearing were initially reduced after lesion, and showed a tendency to recover, especially in the group with the most severe DA depletions ( > 80%). There were no differences between groups neither on day 1 nor on day 7 by grooming, but this behavior increased in all the lesion groups with time. 4. The correlational analyses yielded a positive relationship between the asymmetry in turning and neostriatal DA depletion. Locomotor activity and rearing on day 1 were both negatively correlated with DA depletion. The present results show that a number of behavioral parameters obtained in the open-field are affected by unilateral lesions of the nigro-striatal DA system. The degree of deficit, its time course and relation to lesion size differs among the various behavioral measures. Some of these early behavioral changes after unilateral nigrostriatal lesion are related to DA depletion and should therefore be useful to predict lesion size. 5. Together, these data suggest that the study of such behavioral changes can provide an important tool, to investigate the compensatory mechanisms underlying striatal DA depletion and to understand preclinical states of the Parkinson's disease.