Related Experiment Videos
Oxygen radicals diminish dopamine transporter function in rat striatum
A E Fleckenstein1, R R Metzger, M L Beyeler
1Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
European Journal of Pharmacology
|November 5, 1997
Summary
Reactive oxygen species generated by xanthine oxidase reduce dopamine transporter function by decreasing Vmax. Superoxide dismutase reversed this effect, suggesting a role for reactive oxygen species in methamphetamine
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Dopamine transporter (DAT) function is crucial for regulating dopaminergic neurotransmission.
- Methamphetamine is known to affect DAT function, but the underlying mechanisms are not fully understood.
- Reactive oxygen species (ROS) are implicated in various cellular processes and pathologies.
Purpose of the Study:
- To investigate the in vitro effect of reactive oxygen species on dopamine transporter function.
- To determine the role of superoxide radicals in mediating these effects.
- To explore the potential relevance to methamphetamine-induced neurotoxicity.
Main Methods:
- Striatal synaptosomes were incubated with xanthine oxidase to generate oxygen radicals.
- [3H]dopamine uptake assays were performed to measure DAT function.
- Superoxide dismutase was used as a superoxide radical scavenger to assess its protective effects.
Main Results:
- Xanthine oxidase significantly decreased [3H]dopamine uptake in striatal synaptosomes.
- This decrease in dopamine uptake was attributed to a reduction in Vmax, indicating impaired transporter capacity.
- Concurrent incubation with superoxide dismutase completely abolished the inhibitory effect of xanthine oxidase.
Conclusions:
- Reactive oxygen species, specifically superoxide radicals, diminish dopamine transporter function in vitro.
- These findings suggest that ROS contribute to the impairment of DAT function observed with methamphetamine administration.
- The study highlights a potential mechanism underlying methamphetamine's neurotoxic effects involving oxidative stress.