Progressive alteration of neuronal dopamine transporter activity in a rat injured by an intranigral injection of MPP

MPTP or its metabolite MPP+ are used to produce a Parkinsonism syndrome in a variety of aninial species. The present study describes the effects of intranigral MPP+ administration either at 10 or 40 mug on the neuronal dopamine transporter ( DAT) activity measured in rat striatal synaptosomes at different times after lesion. The 40 mug MPP+ injection induced a maximal toxic effect on day 7. However, 10 mug MPP+ progressively inhibited DA uptake on the injured side. V-mux decreased in a time-dependent manner and the lowest value was observed on day 21 after lesion. At this time, the K. value began to increase and was continuously accentuated until day 45 as compared to the contralateral side. Treatments either with the antioxidant alpha-tocopherol acetate or the MAO inhibitor pargyline, given daily for 7 days after lesion, partially prevented the 40 mug MPP+-induced inhibition of DA uptake. Conversely, both treatments given daily for 21 days after lesion completely prevented the alteration of DAT activity in the ipsilateral striatum induced by 10 mug MPP+. The absence of protection when both treatments were stopped 2 weeks before DA uptake measurement,., indicated that free radicals and DA oxidized products were continuously accumulated and gradually affected the functionality of the DAT, These results demonstrate that a rat intranigral lesion with 10 mug MPP+ led to a progressive impairment of DAT activity. (C) 2002 Elsevier Science B.V. All rights reserved.