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.
Schroeder
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Institute of Medical Psychology, Medical Faculty, Otto-von-Guericke University Magdeburg, Germany.
Kreutz
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Schroeder
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D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000633:toxicity*; D018492:Dopamine Antagonists / Q000378:metabolism; D007150:Immunohistochemistry; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D013134:Spiperone; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D003913:Dextroamphetamine