Doris J Doudet1, James E Holden. 1. Department of Medicine, Division of Neurology and Pacific Parkinson Research Center and TRIUMF (DJD), University of British Columbia, Vancouver, British Columbia, Canada.
Abstract
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.
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.
Authors: Anne M Landau; M Mallar Chakravarty; Campbell M Clark; Athanasios P Zis; Doris J Doudet Journal: Neuropsychopharmacology Date: 2010-10-13 Impact factor: 7.853
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