Amphetamine induces hypermotility in MPTP-lesioned mice.

Two strains of mice (NMRI and C57B1/ 6) were treated with MPTP (within 8 h 4 x 30 mg/kg MPTP, IP) and motility was monitored 10 days later. An acute administration of amphetamine (2.5 mg/kg or 10.0 mg/kg) or apomorphine (0.5 mg/kg or 5.0 mg/kg) led to hypermotility and a dose-dependent increase of stereotyped behavior. Immunocytochemical investigations indicated a substantial loss of tyrosine-hydroxylase immunoreactivity in the basal ganglia which was accompanied by a 15% increase of 3H-spiroperidol binding to a striatal membrane preparation. No difference was found in biochemical and behavioral measures between both mice strains. Thus, MPTP-induced lesions in mice are probably followed by a denervation-like supersensitivity of the dopaminergic system, which might account for the finding that despite a severe degeneration of dopaminergic terminals amphetamine induces hypermotility.