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Inhibition of dopamine uptake by D 2 antagonists: an in vivo study
Author(s) -
BenoitMarand Marianne,
Ballion Bérangère,
Borrelli Emiliana,
Boraud Thomas,
Go Francois
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.07125.x
Subject(s) - dopamine , in vivo , dopamine receptor d2 , pharmacology , neuroscience , chemistry , medicine , psychology , biology , microbiology and biotechnology
J. Neurochem. (2011) 116 , 449–458. Abstract 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.