Inhibition of dopamine uptake by D2 antagonists: An in vivo study
Journal of Neurochemistry. 2010-12-22; 116(3): 449-458
DOI: 10.1111/j.1471-4159.2010.07125.x
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Inhibition of dopamine uptake by D2 antagonists: an in vivo study.
Benoit-Marand M(1), Ballion B, Borrelli E, Boraud T, Gonon F.
Author information:
(1)University of Bordeaux, Bordeaux, France.
D(2)-like antagonists potentiate dopamine release. They also inhibit dopamine
uptake by a mechanism yet to be clarified. Here, we monitored dopamine uptake in
the striatum of anesthetized mice. The dopamine overflow was evoked by brief
electrical stimulation of the medial forebrain bundle (four pulses at 100 Hz)
and was monitored with carbon fiber electrodes combined with continuous
amperometry. The decay phase of evoked overflows reflects dopamine half-life,
which entirely depends on uptake. The D(2)-like antagonists haloperidol and
eticlopride enhanced the half-life by 45% and 48%, respectively, a moderate
effect as compared to the uptake blocker nomifensine (528%). Both D(2)-like
antagonists did not affect dopamine uptake in mice lacking D(2) receptors.
Inhibition of tonic dopamine release by gamma-butyrolactone did not mimic the
enhancing effect of D(2) antagonists on dopamine half-life. However, prolonged
stimulation boosted dopamine uptake and this effect was not observed after
haloperidol treatment or in mice lacking D(2) receptors. Therefore, dopamine
uptake is accelerated in conditions of excessive D(2) stimulation but not finely
tuned in resting conditions. Inhibition of dopamine uptake by D(2) antagonists
synergizes with the potentiation of dopamine release to strongly alter the
phasic dopamine signaling.
© 2010 The Authors. Journal of Neurochemistry © 2010 International Society for
Neurochemistry.
DOI: 10.1111/j.1471-4159.2010.07125.x
PMID: 21128941 [Indexed for MEDLINE]