Abstract: Objective To establish different 6-hydroxydopamine(6-OHDA) lesioned mice model, we evaluated the behavioral, neurochemical and histological effect of different dosage injection of 6-OHDA on motor dysfunction and dopamine denervation. Methods Different doses of 6-OHDA(4 μg, 6 μg, 8 μg, 10 μg) were injected into the right dorsal striatum under the facilitation of stereotactic equipment. The body weight after 6-OHDA injection was observed. Apomorphine-induced rotation and rota-rod test were used to estimate motor impairment. Tyrosine hydroxylase(TH) immunostaining was performed to determine the dopaminergic cell loss. Dopamine(DA) content was determined by HPLC. Results 10 μg 6-OHDA injection induced a temporary weight loss, while as other dose of 6-OHDA had no obvious effect on the body weight of mice. At the 1st week after the injection of 6-OHDA, the positive apomorphine induced rotation was observed and this rotational performance was stable for at least 5 weeks. The mice of 8 μg and 10 μg 6-OHDA injection decreased the latency time on the rota-rod. TH-immunolabeling indicated that the 4 μg and 6 μg 6-OHDA injections reduced the number of 60% DA neurons and 40% fibers, as well as 8 μg and 10 μg 6-OHDA injections reduced the number of 80% DA neurons and 70% fibers. Besides, 6-OHDA injection leads to the significant decrease of striatal DA and its metabolites. The decreased of DA content showed a positive correlation with the injection dosage of 6-OHDA, and a negative correlation with dopamine availability(DOPAC+HVA/DA). Conclusion 4 μg and 6 μg 6-OHDA injection induced partial lesions of the nigrostriatal DA system to mimic the early phases of Parkinson's disease(PD). 8 μg and 10 μg 6-OHDA injection induced completely lesions of the nigrostriatal DA system to mimic the late phases of PD.

Key words: 6-hydroxydopamine, striatum, Parkinson's disease, mice model