Amphetamine distorts stimulation-dependent dopamine overflow: Effects on D2 autoreceptors, transporters, and synaptic vesicle stores

Yvonne Schmitz, Changjoon Lee, Claudia Schmauss, François Gonon, David Sulzer

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

Amphetamine (AMPH) is known to raise extracellular dopamine (DA) levels by inducing stimulation-independent DA efflux via reverse transport through the DA transporter and by inhibiting DA re-uptake. In contrast, recent studies indicate that AMPH decreases stimulation-dependent vesicular DA release. One candidate mechanism for this effect is the AMPH-mediated redistribution of DA from vesicles to the cytosol. In addition, the inhibition of stimulation-dependent release may occur because of D2 autoreceptor activation by DA that is released via reverse transport. We used the D2 receptor antagonist sulpiride and mice lacking the D2 receptor to address this issue. To evaluate carefully AMPH effects on release and uptake, we recorded stimulated DA overflow in striatal slices by using continuous amperometry and cyclic voltammetry. Recordings were fit by a random walk simulation of DA diffusion, including uptake with Michaelis-Menten kinetics, that provided estimates of DA concentration and uptake parameters. AMPH (10 μM) promoted the overflow of synaptically released DA by decreasing the apparent affinity for DA uptake (Km increase from 0.8 to 32 μM). The amount of DA released per pulse, however, was decreased by 82%. This release inhibition was prevented partly by superfusion with sulpiride (47% inhibition) and was reduced in D2 mutant mice (23% inhibition). When D2 autoreceptor activation was minimal, the combined effects of AMPH on DA release and uptake resulted in an enhanced overflow of exocytically released DA. Such enhancement of stimulation-dependent DA overflow may occur under conditions of low D2 receptor activity or expression, for example as a result of AMPH sensitization.

Original languageEnglish
Pages (from-to)5916-5924
Number of pages9
JournalJournal of Neuroscience
Volume21
Issue number16
Publication statusPublished - 2001 Aug 15
Externally publishedYes

Fingerprint

Autoreceptors
Dopamine Agents
Synaptic Vesicles
Amphetamine
Dopamine
Sulpiride
Corpus Striatum
Dopamine Plasma Membrane Transport Proteins

Keywords

  • Amperometry
  • Amphetamine
  • Cyclic voltammetry
  • D2 receptor
  • Dopamine
  • Sensitization
  • Uptake

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Amphetamine distorts stimulation-dependent dopamine overflow : Effects on D2 autoreceptors, transporters, and synaptic vesicle stores. / Schmitz, Yvonne; Lee, Changjoon; Schmauss, Claudia; Gonon, François; Sulzer, David.

In: Journal of Neuroscience, Vol. 21, No. 16, 15.08.2001, p. 5916-5924.

Research output: Contribution to journalArticle

Schmitz, Yvonne ; Lee, Changjoon ; Schmauss, Claudia ; Gonon, François ; Sulzer, David. / Amphetamine distorts stimulation-dependent dopamine overflow : Effects on D2 autoreceptors, transporters, and synaptic vesicle stores. In: Journal of Neuroscience. 2001 ; Vol. 21, No. 16. pp. 5916-5924.
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