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D 3 receptor ligands modulate extracellular dopamine clearance in the nucleus accumbens
Author(s) -
Zapata A.,
Shippenberg T. S.
Publication year - 2002
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 - 10.1046/j.1471-4159.2002.00893.x
Subject(s) - nucleus accumbens , dopamine , microdialysis , chemistry , striatum , extracellular , dopamine transporter , medicine , endocrinology , agonist , dopamine uptake inhibitors , dopamine plasma membrane transport proteins , dopamine receptor d1 , dopamine receptor , receptor , biology , dopaminergic , biochemistry
Abstract An involvement of the D 3 dopamine receptor in the regulation of extracellular dopamine has been suggested. However, the mechanisms mediating this effect are unclear. We have used the technique of no net flux microdialysis under transient conditions to examine the influence of the D 3 ‐preferring agonist (+)‐PD128907 upon extracellular dopamine levels in the nucleus accumbens of the mouse. (+)‐PD 128907 (0.1 mg/kg intraperitoneally) significantly decreased extracellular dopamine. This decrease was associated with a marked increase in the extraction fraction, which suggests an increase in dopamine clearance. The ability of D 3 ‐preferring compounds to modulate dopamine uptake was investigated in vitro using rotating disk electrode voltammetry. (+)‐PD 128907 (10 n m ) significantly increased the initial clearance rate of 3 μ m dopamine in rat nucleus accumbens tissue suspensions. Kinetic analysis revealed no change in the apparent K m of uptake but it showed a 33% increase in V max . In contrast, the D 3 antagonist GR 103691 (10 n m ) significantly decreased dopamine uptake. Consistent with the low levels of D 3 receptors in the dorsal striatum, neither compound affected uptake in tissue suspensions from this brain region. These data indicate that D 3 receptor activation increases dopamine uptake in the nucleus accumbens and suggest that this receptor subtype can regulate extracellular dopamine by modulating the DA transporter activity.