Amphetamine Modulates Excitatory Neurotransmission through Endocytosis of the Glutamate Transporter EAAT3 in Dopamine Neurons

Suzanne M. Underhill, David S. Wheeler, Minghua Li, Spencer D. Watts, Susan L. Ingram, Susan G. Amara

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Amphetamines modify the brain and alter behavior through mechanisms generally attributed to their ability to regulate extracellular dopamine concentrations. However, the actions of amphetamine are also linked to adaptations in glutamatergic signaling. We report here that when amphetamine enters dopamine neurons through the dopamine transporter, it stimulates endocytosis of an excitatory amino acid transporter, EAAT3, in dopamine neurons. Consistent with this decrease in surface EAAT3, amphetamine potentiates excitatory synaptic responses in dopamine neurons. We also show that the process of internalization is dynamin- and Rho-mediated and requires a unique sequence in the cytosolic C terminus of EAAT3. Introduction of a peptide based on this motif into dopamine neurons blocks the effects of amphetamine on EAAT3 internalization andits action on excitatory responses. These data indicate that the internalization of EAAT3 triggered byamphetamine increases glutamatergic signaling and thus contributes to the effects of amphetamine on neurotransmission.

Original languageEnglish (US)
Pages (from-to)404-416
Number of pages13
JournalNeuron
Volume83
Issue number2
DOIs
StatePublished - Jul 16 2014

ASJC Scopus subject areas

  • Neuroscience(all)

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