Abstract

Pramipexole, an agonist for dopamine (DA) at D₂/D₃-receptors, has been used to treat both early and advanced Parkinson’s disease (PD). The present study was to evaluate the neuroprotective effect of pramipexole (PPX) in a DA neuron degeneration model of PD induced by rotenone. Thirty six male mice were used and divided into 3 equal groups. The first group, the control group, received only sunflower oil intraperitoneally (i.p.) once daily at a volume of 4 ml/kg for 49 days. The second group was given rotenone (2 mg/kg/day; i.p.) for 49 days. The third group was given pramipexole (1 mg/kg, i.p.) which was administered 30 min prior to rotenone (2 mg/kg/day; i.p.) for 49 days. Behavioral tests were performed a day prior to drug administration and then once weekly along the duration of drugs or vehicle administration.At the end of the 49 days all animals were sacrificed and their midbrains were subjected to immunohistochemical analysis for dopaminergic neurons staining for anti-TH antibodies. In addition midbrain tissues were obtained for biochemical measurements. Behavioural test showed improvement of mice activity in the pramipexole group.Immunohistochemistry results revealed that the rotenone-induced loss of TH-immunopositive neurons (DA neurons) in the SNpc was inhibited by the pramipexole treatment. Biochemical measurements demonstrated that PPX treatment significantly reversed the rotenone-induced decrease in midbrain DA level. In addition pramipexole attenuate the decrease in total antioxidant capacity as well as the increase in the malondialdehyde level and nitric oxide generation induced by chronic rotenone administration. These results suggest a possible beneficial effect of pramipexole against the PD-like disorder induced by the chronic intraperitoneal administration of rotenone. This neuroprotective effect mediated even in part by the antioxidant properties of pramipexole.

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