Synaptic concentration of dopamine in rat striatal slices in relationship to [3H]raclopride binding to the dopamine D2 receptor
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Thein vivo binding of dopamine (DA) radioligands to D2 receptors can be affected by competition with endogenous dopamine. In the present study, we used a brain slice preparation that provides more controlled conditions thanin vivo preparations in order to examine the relationship between synaptic DA and the binding of [3H]raclopride to D2 receptors. We also estimated the synaptic DA concentration in rat striatal slices by determining the changes in [3H]raclopride binding. To correlate the changes in [3H]raclopride binding with the concentration of synaptic DA, the kinetic parameters were determined. [3H]Raclopride reached equilibrium binding conditions within two hours. The Ki value for DA in inhibiting [3H]raclopride binding was about 2.2nM. The increase in synaptic DA evoked by electrical stimulation decreased the striatal binding of [3H]raclopride in a frequency-dependent manner. Increases in the DA concentration evoked by amphetamine (AMPH) or cocaine decreased [3H]raclopride binding by 74% or 20% respectively, corresponding to increases in the synaptic DA concentrations of 1.6nM or 0.6nM, respectively. Pargyline also decreased [3H]raclopride binding by 36% corresponding at a concentration of 1.2nM. In contrast, the depletion of synaptic DA by α-methyl-p-tyrosine (α-MpT) increased the specific binding of [3H]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 [3H]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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- Synaptic concentration of dopamine in rat striatal slices in relationship to [3H]raclopride binding to the dopamine D2 receptor
Archives of Pharmacal Research
Volume 23, Issue 4 , pp 360-366
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