Amphetamine-induced locomotor activity is reduced in mice following MPTP treatment but not following selegiline/MPTP treatment.
MPTP treatment has been used in mice to cause dopaminergic neuronal cell loss and subsequent behavioral abnormalities. As such, this animal model is often used as a method for the characterization of putative novel therapeutics for disease states characterized by dopamine loss, such as Parkinson's disease. Previous reports of behavioral abnormalities in mice following MPTP intoxication, however, have been conflicting. For example, open field spontaneous activity has been reported to increase, decrease or not change in MPTP treated mice. Accordingly, a more robust and direct functional measure of MPTP-induced central dopamine depletion is needed. In the present manuscript, we report on the characterization of amphetamine-induced locomotor activity as a sensitive functional endpoint for dopamine loss following MPTP treatment. We found that the amphetamine-induced locomotor activity of C57BL/6 mice was reduced in a dose-dependent manner following treatment with MPTP. This reduction of activity was associated with decreases in central dopamine levels. Further, the potential for use of this endpoint to evaluate putative therapeutics is exemplified by the amelioration of these effects following pre-treatment with the MAO-B inhibitor selegiline.
West
Brian D
BD
Neuroscience Drug Discovery, Merck Research Laboratories, P.O. Box 4, WP44E-200, West Point, PA 19486, USA.
Shughrue
Paul J
PJ
Vanko
Amy E H
AE
Ransom
Richard W
RW
Kinney
Gene G
GG
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology*
D018696:Neuroprotective Agents; D012642:Selegiline; D016202:N-Methylaspartate; D000661:Amphetamine; D004298:Dopamine