Abstract
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Objectives Amphetamine is known to cause a transient surge in extracellular dopamine (DA) and a lasting decrease in binding potential (BP) measured with PET. We introduce a method to estimate the amount of bound DA due to intravenous amphetamine administration and examine how this contributes to our understanding of mechanisms of amphetamine-induced dopamine release (DArel).
Methods Healthy subjects without neuropsychiatric disorders (n=25; 13F; Age: 22.5 ± 5.5 years) had two high specific activity (SA) [11C]raclopride scans with i.v. saline and amphetamine (0.5 mg/kg), and one low SA scan. The density of available dopamine D2/3 receptors (Bmax'), dissociation constant (KD), and BP were obtained by bolus-plus-infusion transformation (BPIT; JNM in press) in anterior and posterior putamen and caudate nucleus (aPu, pPu, aCN, and pCN) and ventral striatum (vS). Bound DA was given as the y-value of the line connecting Bmax and baseline BP at amphetamine BP on a Eadie-Hofstee plot (x-axis: bound/free; y-axis: bound in pmol/mL).
Results Bmax' showed a strong region effect (p<0.001, ANOVA; pPu>aPu>aCN>vS>pCN, paired t-test) while KD did not significantly differ by sub-regions. DArel and bound DA also showed strong region effects (p<0.001, ANOVA; pPu>(aPu=vS)>(pCN=aCN), paired t-test). On scatter plots of DArel versus bound DA, pPu formed a distinctive linear cluster of higher DArel and bound DA with a lower slope (=3.0; R2=0.737) compared to the other four regions which formed a separate linear cluster (slope = 4.6; R2=0.790; p<0.001, test for slopes).
Conclusions A method was introduced for estimation of bound DA after amphetamine administration. The results suggested bound DA relative to DArel (= bound DA/Bmax') was greater in pPu than other four striatum subdivisions. Although the explanations for these findings must be sought, measurements of bound DA may be useful for understanding of neuropsychiatric conditions, including schizophrenia in which changes in DArel are suggested