title: Synaptic concentration of dopamine in rat striatal slices in relationship to [3H]raclopride binding to the dopamine D2 receptor.
abstract: The in 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 than in 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 2.2 nM. 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 1.6 nM or 0.6 nM, respectively. Pargyline also decreased [3H]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 [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.
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, Korea.
authors.forename: M H
authors.initials: MH
authors.lastname: Park
authors.forename: E H
authors.initials: EH
authors.lastname: Park
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000737:chemistry*; D004298:Dopamine / Q000032:analysis*; D018492:Dopamine Antagonists / Q000378:metabolism*; D004558:Electric Stimulation; D008297:Male; D020891:Raclopride / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013569:Synapses / Q000737:chemistry*
chemical_list: D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D020891:Raclopride; D004298:Dopamine