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Related Experiment Videos

Methamphetamine-induced rapid and reversible changes in dopamine transporter function: an in vitro model.

V Sandoval1, E L Riddle, Y V Ugarte

  • 1Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|February 13, 2001
PubMed
Summary

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A single methamphetamine (METH) injection reduces dopamine transporter (DAT) activity. This study shows that METH directly applied to synaptosomes mimics this effect, suggesting phosphorylation as a key mechanism.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Methamphetamine (METH) rapidly and reversibly decreases dopamine transporter (DAT) activity after a single injection.
  • This effect is not due to residual drug or altered DAT ligand binding.

Purpose of the Study:

  • To investigate the mechanism behind METH's effect on DAT activity.
  • To determine if direct METH application to synaptosomes replicates in vivo findings.

Main Methods:

  • Incubation of striatal synaptosomes with METH and related compounds.
  • Assessing DAT activity and WIN35428 binding.
  • Measuring membrane potential using [(3)H]tetraphenylphosphonium.
  • Utilizing a protein kinase C inhibitor (NPC15437).

Main Results:

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  • Direct METH incubation decreased DAT activity, similar to ex vivo results, without affecting WIN35428 binding.
  • 3,4-methylenedioxymethamphetamine mimicked METH's effect, but cocaine and methylphenidate did not.
  • METH-induced DAT activity reduction was independent of membrane potential changes.
  • NPC15437 attenuated the METH-induced DAT activity decline, suggesting a role for phosphorylation.

Conclusions:

  • The in vitro synaptosome incubation model effectively replicates the rapid and reversible effects of METH on DAT activity observed in vivo.
  • Phosphorylation, potentially mediated by protein kinase C, is implicated in the mechanism of METH-induced DAT inhibition.