The present study examines the motor responses of 10- to 12-month-old, male C57 mice that were either given intraperitoneal (IP)
injections of
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (
MPTP; 30 mg/kg per day) or vehicle for 10 consecutive days, followed by IP
injections of
levodopa (200 mg/kg) plus
carbidopa (25 mg/kg). Five days of
MPTP exposure resulted in the Straub tail phenomenon and pronounced
hypokinesia. However, during the next 5 days, motor activity returned to baseline, even with continued
MPTP treatment. After 10 to 14 days of rest, all mice were then treated with
levodopa/
carbidopa twice daily for multiple, consecutive days. However, only the previously
MPTP-treated animals became hyperkinetic, as compared to
levodopa-treated control animals that were not previously exposed to
MPTP. Abnormal activity included scratching, running, gnawing, and jumping movements. Hyperactivity lasted for approximately 2 hours after each
levodopa injection and then returned to baseline, but the amount of
hyperkinesia increased with additional days of
levodopa treatment, even though the daily
levodopa dose was not changed. These results demonstrate that
levodopa can cause reproducible hyperactivity in mice that were previously exposed to
MPTP.