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Title: | Estimating the effect of endogenous dopamine on baseline [11C]‐(+)‐PHNO binding in the human brain |
Authors: | Caravaggio, Fernando Kegeles, Lawrence S. Wilson, Alan A. Remington, Gary Borlido, Carol Mamo, David Graff-Guerrero, Ariel |
Keywords: | Dopamine Schizophrenia Antipsychotic drugs |
Issue Date: | 2016 |
Publisher: | Infomed |
Citation: | Caravaggio, F., Kegeles, L. S., Wilson, A. A., Remington, G., Borlido, C., Mamo, D. C., & Graff‐Guerrero, A. (2016). Estimating the effect of endogenous dopamine on baseline [11C]‐(+)‐PHNO binding in the human brain. Synapse, 70(11), 453-460. |
Abstract: | Endogenous dopamine (DA) levels at dopamine D2/3 receptors (D2/3R) have been quantified in the living human brain using the agonist radiotracer [11C]-(1)-PHNO. As an agonist radiotracer, [11C]- (1)-PHNO is more sensitive to endogenous DA levels than antagonist radiotracers. We sought to determine the proportion of the variance in baseline [11C]-(1)-PHNO binding to D2/3Rs which can be accounted for by variation in endogenous DA levels. This was done by computing the Pearson’s coefficient for the correlation between baseline binding potential (BPND) and the change in BPND after acute DA depletion, using previously published data. All correlations were inverse, and the proportion of the variance in baseline [11C]-(1)-PHNO BPND that can be accounted for by varia- tion in endogenous DA levels across the striatal subregions ranged from 42-59%. These results indicate that lower baseline values of [11C]-(1)-PHNO BPND reflect greater stimulation by endoge- nous DA. To further validate this interpretation, we sought to examine whether these data could be used to estimate the dissociation constant (Kd) of DA at D2/3R. In line with previous in vitro work, we estimated the in vivo Kd of DA to be around 20 nM. In summary, the agonist radiotracer [ 11C]-(1)-PHNO can detect the impact of endogenous DA levels at D2/3R in the living human brain from a single baseline scan, and may be more sensitive to this impact than other commonly employed radiotracers. |
URI: | https://www.um.edu.mt/library/oar//handle/123456789/23952 |
Appears in Collections: | Scholarly Works - FacM&SPsy |
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