Fig. 4.

Continuous MPTP administration induces neuronal inclusions and a dopamine-dependent behavioral phenotype. (a and b) Inclusion bodies in the substantia nigra from mice treated for 28 days with continuous MPTP infusions (30 mg/kg daily). Inclusions were stained for ubiquitin (a) and α-synuclein (b). (Scale bars, 120 μm at Left and 35 μm at Right.) (c and d) Electron micrographs of inclusions observed 72 h (c) or 30 days (d) of MPTP infusion. (Scale bars, 0.1 μm.) Note that similar inclusions were observed in the locus coeruleus (Fig. 12). (e and f) Open field behaviors of mice infused continuously with control solution or intermediate (5 mg/kg daily) and high doses of MPTP (30 mg/kg daily). Suppression of open field activity (e) and rearing (f) by continuous MPTP administration was reversed by the mixed dopamine agonist apomorphine (APO). Asterisks indicate statistically significant differences from control mice (see Movies 1–3, which are published as supporting information on the PNAS web site).