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Title: Estimating endogenous dopamine levels at D2 and D3 receptors in humans using the agonist radiotracer [11C]-(+)-PHNO
Authors: Caravaggio, Fernando
Nakajima, Shinichiro
Borlido, Carol
Remington, Gary
Gerretsen, Philip
Wilson, Alan
Houle, Sylvain
Menon, Mahesh
Mamo, David
Graff-Guerrero, Ariel
Keywords: Dopamine
Depression, Mental
Issue Date: 2014
Publisher: Nature Publishing Group
Citation: Caravaggio, F., Nakajima, S., Borlido, C., Remington, G., Gerretsen, P., Wilson, A., ... & Graff-Guerrero, A. (2014). Estimating endogenous dopamine levels at D2 and D3 receptors in humans using the agonist radiotracer [11C]-(+)-PHNO. Neuropsychopharmacology, 39(12), 2769-2776.
Abstract: Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D2/3 receptors (D2/3R) in humans in vivo. Our group has developed [11C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D3R. Thus, the use of [11C]-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D2/3R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D3R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a [11C]-(+)-PHNO PET scan under baseline conditions and another under acute endogenous dopamine depletion achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg). [11C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D2R-rich regions (caudate and putamen), mixed D2/3R-rich regions (ventral striatum and globus pallidus), and extrastriatal D3R-rich regions (hypothalamus and ventral pallidum). Dopamine depletion decreased self-reported vigor, which was correlated with the reduction in dopamine levels in the globus pallidus. [11C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in neuropsychiatric populations.
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