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Synaptic concentration of dopamine in rat striatal slices in relationship to [H-3]raclopride binding to the dopamine D-2 receptor

Authors
Park, MHPark, EH
Issue Date
Aug-2000
Publisher
PHARMACEUTICAL SOCIETY KOREA
Keywords
dopamine; [H-3]raclopride; striatal slice; electrical stimulation; amphetamine; alpha-methyl-p-tyrosine
Citation
ARCHIVES OF PHARMACAL RESEARCH, v.23, no.4, pp.360 - 366
Journal Title
ARCHIVES OF PHARMACAL RESEARCH
Volume
23
Number
4
Start Page
360
End Page
366
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/16747
DOI
10.1007/BF02975448
ISSN
0253-6269
Abstract
The in vivo binding of dopamine (DA) radioligands to D-2 receptors can be affected by competition with endogenous dopamine. In the present study, we used a brain slice preparation that provides more controlled conditions than in vivo preparations in order to examine the relationship between synaptic DA and the binding of [H-3]raclopride to D-2 receptors. We also estimated the synaptic DA concentration in rat striatal slices by determining the changes in [H-3]raclopride binding. To correlate the changes in [H-3]raclopride binding with the concentration of synaptic DA, the kinetic parameters were determined. [H-3]Raclopride reached equilibrium binding conditions within two hours. The K-i value for DA in inhibiting [H-3]raclopride binding was about 2.2 nM. The increase in synaptic DA evoked by electrical stimulation decreased the striatal binding of [H-3]raclopride in a frequency-dependent manner. Increases in the DA concentration evoked by amphetamine (AMPH) or cocaine decreased [H-3]raclopride binding by 74% or 20%, respectively, corresponding to increases in the synaptic DA concentrations of 1.6 nM or 0.6 nM, respectively. Pargyline also decreased [H-3]raclopride binding by 36% corresponding at a concentration of 1.2 nM. In contrast, the depletion-of synaptic DA by alpha-methyl-p-tyrosine (alpha-MpT) increased the specific binding of [H-3]raclopride by 43% when the DA concentration was decreased to 0.7 nM. The changes in the DA concentration at the synapse were responsible for the changes in the striatal binding of [H-3]raclopride. The values calculated in this study may therefore approximate the changes in the synaptic DA concentration in rat striatal slices following manipulation.
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