Histochemical, biochemical and behavioural consequences of MPTP treatment in C-57 black mice

The histochemical, biochemical and behavioural consequences of MPTP administration in C-57 black mice was assessed 0.5 h, 24 h and 7 days after the last injection of this drug administered daily for 10 days during a 12 day period (30 mg/kg/injection or vehicle). A slight but significant impairment of open field performance was observed at 0.5 h after the last injection of MPTP while a facilitation of locomotory behaviour was observed only in the 24 h post-injection group. Striatal dopamine levels were reduced to 14, 18 and 27% of control levels in the 0.5 h, 24 h and 7 day post-MPTP treated groups, respectively. Histochemical assessment was in agreement with the biochemical assay results in that all MPTP treated animals showed severe depletion of striatal terminal fields. Other terminal fields were occasionally affected by MPTP treatment and only rarely was any change in the fluorescence or morphology of nigral cell bodies seen. Accumulation of amines in the degenerating amine-containing axons which traverse the lateral hypothalamus was not seen in any of the MPTP treated animals. These results indicate that, in the C-57 black mouse, MPTP causes a depletion of striatal dopamine without causing nigral cell loss or axon swelling as is observed with other experimental treatments such as 6-hydroxydopamine. Consistent with this is the behavioural data, indicating that severe deficits in motor function which are associated with nigrostriatal cell loss were not seen. We conclude that the inability of MPTP to produce motor function impairment in various species is related to its failure to produce true degenerative changes in nigrostriatal neurons which include amine accumulation in the degenerating axons and cell loss in the substantia nigral complex.