Raclopride studies of dopamine release: dependence on presynaptic integrity.
BACKGROUND
Raclopride and dopamine (DA) compete for in vivo binding to the D(2) receptors. Thus, measurements of raclopride binding provide a method to evaluate endogenous release in a variety of conditions. Amphetamine elicits DA release, provoking a rapid increase in synaptic DA and leading to a reduction in raclopride binding, which outlasts the temporary increase in extracellular DA concentrations by several hours. The mechanism responsible for the decrease in raclopride binding is still unclear.


METHODS
We used a multiple ligand concentration receptor assay method in normal monkeys and in monkeys with varying degrees of lesion of the DA nigrostriatal terminals to measure the density and affinity of D(2) receptors after methamphetamine challenge.


RESULTS
The reduced raclopride binding can be accounted for by a decreased affinity of the ligand to the receptors. There is a direct, nonlinear relationship between the presynaptic storage capacity and the change in raclopride binding after methamphetamine.


CONCLUSIONS
This observation may bear important implications for the understanding of diseases such as schizophrenia in which the marked increase in amphetamine-induced displacement of raclopride compared with normal control subjects suggests increased release of DA from presynaptic stores and potential abnormalities in presynaptic DA function.
Doudet
Doris J
DJ
Department of Medicine, Division of Neurology and Pacific Parkinson Research Center and TRIUMF (DJD), University of British Columbia, Vancouver, British Columbia, Canada.
Holden
James E
JE
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005462:Fluorine Radioisotopes; D008253:Macaca mulatta; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D020891:Raclopride / Q000494:pharmacology*; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism; D014055:Tomography, Emission-Computed; D050492:Vesicular Biogenic Amine Transport Proteins
D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D005462:Fluorine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D017448:Receptors, Dopamine D2; D050492:Vesicular Biogenic Amine Transport Proteins; C032811:dihydrotetrabenazine; D020891:Raclopride; D004295:Dihydroxyphenylalanine; D004298:Dopamine; D013747:Tetrabenazine