ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract : Presynaptic D2 dopamine (DA) autoreceptors,which are well known to modulate DA release, have recently been shown toregulate DA transporter (DAT) activity. To examine the effects ofD2 DA receptor deficiency on DA release and DAT activity in dorsalstriatum, we used mice genetically engineered to have two(D2+/+), one (D2+/-), or no(D2-/-) functional copies of the gene coding for theD2 DA receptor. In vivo microdialysis studies demonstrated thatbasal and K+-evoked extracellular DA concentrations were similar inall three genotypes. However, using in vivo electrochemistry, theD2-/- mice were found to have decreased DAT function,i.e., clearance of locally applied DA was decreased by 50% relative to that inD2+/+ mice. In D2+/+ mice, but notD2-/- mice, local application of the D2-likereceptor antagonist raclopride increased DA signal amplitude, indicatingdecreased DA clearance. Binding assays with the cocaine analogue[3H]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 D2 DA receptor subtype modulates activity of the striatal DAT.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1999.0720148.x
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