The AAPS Journal

, Volume 7, Issue 4, pp E847-E851

First online:

Role of monoamine transporters in mediating psychostimulant effects

  • Evan L. RiddleAffiliated withDepartment of Pharmacology and Toxicology, University of Utah
  • , Annette E. FleckensteinAffiliated withDepartment of Pharmacology and Toxicology, University of Utah
  • , Glen R. HansonAffiliated withDepartment of Pharmacology and Toxicology, University of Utah Email author 

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Monoamine transporters such as the dopamine (DA) transporter (DAT) and the vesicular monoamine transporter-2 (VMAT-2) are critical regulators of DA disposition within the brain. Alterations in DA disposition can lead to conditions such as drug addiction, Parkinson’s disease, and schizophrenia, a fact that underscores the importance of understanding DAergic signaling. Psychostimulants alter DAergic signaling by influencing both DAT and VMAT-2, and although the effects of these drugs result in increased levels of synaptic DA, the mechanisms by which this occurs and the effects that these drugs exert on DAT and VMAT-2 vary. Many psychostimulants can be classified as releasers (ie, amphetamine analogs) or uptake blockers (ie, cocaine-like drugs) based on the mechanism of their acute effects on neurotransmitter flux through the DAT. Releasers and uptake blockers differentially modulate the activity and subcellular distribution of monoamine transporters, a phenomenon likely related to the neurotoxics potential of these drugs to DAergic neurons. This article will review some of the recent findings whereby releasers and uptake blockers alter DAT and VMAT-2 activity and how these alterations may be involved in neurotoxicity, thus providing insight on the neuro-degeneration observed in Parkinson’s disease.


dopamine transporter vesicular monoamine transporter-2 amphetamine cocaine methylphenidate Parkinson’s disease