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Related Experiment Videos

Methamphetamine rapidly decreases vesicular dopamine uptake.

J M Brown1, G R Hanson, A E Fleckenstein

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

Journal of Neurochemistry
|May 9, 2000
PubMed
Summary

Methamphetamine rapidly impairs vesicular dopamine uptake in brain cells, a key process for regulating dopamine levels. This dysfunction in vesicular monoamine transporter function may contribute to long-term damage from methamphetamine use.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Vesicular sequestration regulates cytoplasmic monoamine levels, including dopamine.
  • Increased cytoplasmic dopamine may link to methamphetamine-induced dopaminergic deficits via vesicular monoamine transporter (VMAT) dysfunction.

Purpose of the Study:

  • To investigate alterations in striatal vesicular dopamine uptake following methamphetamine administration.

Main Methods:

  • Assessed striatal vesicular dopamine uptake and dihydrotetrabenazine binding in response to methamphetamine.
  • Evaluated the persistence, neuronal specificity (dopamine vs. serotonin), and drug-dependency of the observed effects.

Main Results:

  • Multiple methamphetamine administrations caused a rapid (within 1 hour) decrease in vesicular dopamine uptake and dihydrotetrabenazine binding.

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  • This effect persisted for at least 24 hours and was specific to dopaminergic neurons.
  • The observed reduction was independent of residual methamphetamine levels.

    • Conclusions:

    • Methamphetamine acutely impairs vesicular monoamine transporter function in dopaminergic neurons.
    • This rapid disruption of vesicular dopamine uptake may underlie the neurotoxic effects of methamphetamine.