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Amphetamine induces hypermotility in MPTP-lesioned mice
U Schroeder1, M R Kreutz, H Schroeder
1Institute of Medical Psychology, Medical Faculty, Otto-von-Guericke University Magdeburg, Germany.
Abstract:
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.
Insights
MPTP treatment caused significant dopamine system damage in mice, leading to denervation supersensitivity. This explains why amphetamine still induced hypermotility despite severe dopaminergic terminal degeneration.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin that selectively damages dopaminergic neurons.
- Dopaminergic system dysfunction is implicated in movement disorders like Parkinson's disease.
Purpose of the Study:
- To investigate the behavioral and neurochemical effects of MPTP in two mouse strains.
- To explore the dopaminergic system's response to MPTP-induced neurodegeneration.
Main Methods:
- Two mouse strains (NMRI and C57BL/6) were administered MPTP.
- Motility and stereotyped behavior were assessed after amphetamine or apomorphine challenge.
- Tyrosine-hydroxylase immunoreactivity and dopamine receptor binding were analyzed.
Main Results:
- MPTP treatment caused substantial loss of tyrosine-hydroxylase immunoreactivity in the basal ganglia.
- Amphetamine and apomorphine induced dose-dependent hypermotility and stereotyped behavior.
- A 15% increase in 3H-spiroperidol binding was observed, suggesting receptor supersensitivity.
- No significant differences were found between the two mouse strains.
Conclusions:
- MPTP-induced neurodegeneration in mice leads to denervation-like supersensitivity of the dopaminergic system.
- This supersensitivity may explain the persistent behavioral responses to dopaminergic drugs despite severe neuronal damage.