Abstract
Reactive oxygen species decrease dopamine transporter (DAT) functionin vitro. Because of this, and the finding that METH administration causes oxygen radical formation in vivo, the effects of METH administration on DAT activity in rat striatum were investigated. A single METH injection caused a dose-dependent (0–15 mg/kg) decrease in [3H]dopamine uptake into striatal synaptosomes prepared 1 h after METH administration; an effect attributable to a decreased V max of [3H]dopamine uptake. Similarly, multiple high-dose administrations of METH (10 mg/kg/dose; four doses at 2-h intervals) decreased DAT function. The decreases in DAT activity after either single or multiple METH administrations were reversed 24 h after treatment. [3H]5HT transport into striatal synaptosomes was also affected by METH treatment. Taken together, these data suggest that METH decreases DAT activity, perhaps through a reactive oxygen species-mediated mechanism. These findings may have important implications regarding the role of oxidative events in the physiological regulation of monoaminergic systems.
Footnotes
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Send reprint requests to: Annette E. Fleckenstein, Ph.D., Department of Pharmacology and Toxicology, 112 Skaggs Hall, University of Utah, Salt Lake City, UT 84112.
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↵1 This research was supported by grants DA 00869, DA 04222 and DA 05780 from the National Institute on Drug Abuse.
- Abbreviations:
- DAT
- dopamine transporter
- 5HT
- 5-hydroxytryptamine
- METH
- methamphetamine
- ROS
- reactive oxygen species
- TPH
- tryptophan hydroxylase
- Received December 23, 1996.
- Accepted April 7, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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