Long-term effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal dopamine content in young and mature mice.

Long-term effects of MPTP on striatal dopamine (DA) content and the influence of aging on the recovery were investigated in mice. Male C57BL/6J mice, young (2-month-old) and mature (10-month-old), were used. Two different dosage schedules of MPTP, i.e., 4 doses subcutaneous injections of 20 mg/kg each, and 4 doses subcutaneous injections of 40 mg/kg each, were given to both young and mature mice at 12-h intervals. Assays of striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) content were performed 1 week, 1 month, 2 months, and 3 months after the last injection of MPTP. MPTP produced a marked reduction (-75% to -80%) of striatal DA content in both young and mature mice 1 week after the last injection of MPTP. In young mice, the striatal DA content showed a partial recovery in the subsequent stages studied. In contrast, no apparent recovery occurred in mature mice until as long as 3 months after the last injection. The results suggest that mice have a capacity for partial recovery of the striatal DA contents which was depleted by MPTP, and this capacity for recovery appears to be impaired in mature mice.