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Dopamine D 2 Receptor‐Deficient Mice Exhibit Decreased Dopamine Transporter Function but No Changes in Dopamine Release in Dorsal Striatum
Author(s) -
Dickinson Shelly D.,
Sabeti Jilla,
Larson Gaynor A.,
Giardina Karen,
Rubinstein Marcelo,
Kelly Michele A.,
Grandy David K.,
Low Malcolm J.,
Gerhardt Greg A.,
Zahniser Nancy R.
Publication year - 1999
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.1471-4159.1999.0720148.x
Subject(s) - dopamine , striatum , dopamine transporter , dopamine plasma membrane transport proteins , dopamine receptor d1 , chemistry , dopamine receptor , dorsum , medicine , endocrinology , neuroscience , dopaminergic , biology , anatomy
Abstract : Presynaptic D 2 dopamine (DA) autoreceptors,which are well known to modulate DA release, have recently been shown toregulate DA transporter (DAT) activity. To examine the effects ofD 2 DA receptor deficiency on DA release and DAT activity in dorsalstriatum, we used mice genetically engineered to have two(D 2 +/+ ), one (D 2 +/‐ ), or no(D 2 ‐/‐ ) functional copies of the gene coding for theD 2 DA receptor. In vivo microdialysis studies demonstrated thatbasal and K + ‐evoked extracellular DA concentrations were similar inall three genotypes. However, using in vivo electrochemistry, theD 2 ‐/‐ mice were found to have decreased DAT function,i.e., clearance of locally applied DA was decreased by 50% relative to that inD 2 +/+ mice. In D 2 +/+ mice, but notD 2 ‐/‐ mice, local application of the D 2 ‐likereceptor antagonist raclopride increased DA signal amplitude, indicatingdecreased DA clearance. Binding assays with the cocaine analogue[ 3 H]WIN 35,428 showed no genotypic differences in either density oraffinity of DAT binding sites in striatum or substantia nigra, indicating thatthe differences seen in DAT activity were not a result of decreased DATexpression. These results further strengthen the idea that the D 2 DA receptor subtype modulates activity of the striatal DAT.