JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Metzger, R. R.
Right arrow Articles by Fleckenstein, A. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Metzger, R. R.
Right arrow Articles by Fleckenstein, A. E.

Vol. 295, Issue 3, 1077-1085, December 2000

Methamphetamine-Induced Rapid Decrease in Dopamine Transporter Function: Role of Dopamine and Hyperthermia1,2

Ryan R. Metzger, Heather M. Haughey, Diana G. Wilkins, James W. Gibb , Glen R. Hanson and Annette E. Fleckenstein

Department of Pharmacology and Toxicology (H.M.H., D.G.W., J.W.G., G.R.H., A.E.F.) and Program in Neuroscience (R.R.M., J.W.G., G.R.H., A.E.F.), University of Utah, Salt Lake City, Utah

Single and multiple high-dose administrations of methamphetamine (METH) differentially decrease dopamine (DA) transporter (DAT) function, as assessed by measuring [3H]DA uptake into rat striatal synaptosomes prepared 1 h after treatment. Prevention of METH-induced hyperthermia attenuated the decrease in DAT activity induced by multiple injections of the stimulant. Likewise, this decrease was attenuated by previous depletion of striatal DA levels using alpha -methyl-p-tyrosine (alpha MT) or pretreatment with the D1 and D2 antagonists SCH-23390 and eticlopride, respectively. However, METH-induced hyperthermia was also blocked by alpha MT and eticlopride. Reinstatement of hyperthermia to alpha MT- or eticlopride-pretreated rats partially restored the METH-induced decrease in DAT activity. In contrast, neither prevention of METH-induced hyperthermia depletion of DA, nor DA antagonists altered the decrease in DAT function induced by a single administration of METH. Pretreatment with the antioxidant N-t-butyl-alpha -phenylnitrone prevented part of the decrease in DAT function associated with multiple, but not a single, METH injections. Although not tested directly, additional data presented here suggest that the reduction in DAT activity induced by a single METH administration constitutes a part of the total reduction observed immediately after multiple administrations. Taken together, the results indicate that DA, hyperthermia, and oxygen radicals contribute to a component of the rapid decrease in DAT function induced by multiple injections of METH but do not appear to be associated with the reduction induced by a single administration of the stimulant.

1 This study was supported by U.S. Public Health Service Grants DA05859, DA11389, and DA00869.

2 This work was presented in part at the 29th Annual Meeting of the Society for Neuroscience; 1999 Oct 23-28; Miami Beach, FL.

0022-3565/00/2953-1077$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
G. C. Hadlock, A. J. Baucum II, J. L. King, K. A. Horner, G. A. Cook, J. W. Gibb, D. G. Wilkins, G. R. Hanson, and A. E. Fleckenstein
Mechanisms Underlying Methamphetamine-Induced Dopamine Transporter Complex Formation
J. Pharmacol. Exp. Ther., April 1, 2009; 329(1): 169 - 174.
[Abstract] [Full Text] [PDF]

Home page
 J PsychopharmacolHome page
J. L. Cornish, K. J. Clemens, M. R. Thompson, P. D. Callaghan, B. Dawson, and I. S. McGregor
High ambient temperature increases intravenous methamphetamine self-administration on fixed and progressive ratio schedules in rats
J Psychopharmacol, January 1, 2008; 22(1): 100 - 110.
[Abstract] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
E. A. Reese, J. R. Bunzow, S. Arttamangkul, M. S. Sonders, and D. K. Grandy
Trace Amine-Associated Receptor 1 Displays Species-Dependent Stereoselectivity for Isomers of Methamphetamine, Amphetamine, and Para-Hydroxyamphetamine
J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 178 - 186.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. M. Thomas and D. M. Kuhn
Cyclooxygenase-2 Is an Obligatory Factor in Methamphetamine-Induced Neurotoxicity
J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 870 - 876.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. M. Thomas, P. D. Walker, J. A. Benjamins, T. J. Geddes, and D. M. Kuhn
Methamphetamine Neurotoxicity in Dopamine Nerve Endings of the Striatum Is Associated with Microglial Activation
J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 1 - 7.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. J. Baucum II, K. S. Rau, E. L. Riddle, G. R. Hanson, and A. E. Fleckenstein
Methamphetamine Increases Dopamine Transporter Higher Molecular Weight Complex Formation via a Dopamine- and Hyperthermia-Associated Mechanism
J. Neurosci., March 31, 2004; 24(13): 3436 - 3443.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Sorkina, S. Doolen, E. Galperin, N. R. Zahniser, and A. Sorkin
Oligomerization of Dopamine Transporters Visualized in Living Cells by Fluorescence Resonance Energy Transfer Microscopy
J. Biol. Chem., July 18, 2003; 278(30): 28274 - 28283.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
J. P. Hansen, E. L. Riddle, V. Sandoval, J. M. Brown, J. W. Gibb, G. R. Hanson, and A. E. Fleckenstein
Methylenedioxymethamphetamine Decreases Plasmalemmal and Vesicular Dopamine Transport: Mechanisms and Implications for Neurotoxicity
J. Pharmacol. Exp. Ther., March 1, 2002; 300(3): 1093 - 1100.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2000 by the American Society for Pharmacology and Experimental Therapeutics.