Estimating endogenous dopamine levels at D 2 and D 3 receptors in humans using the agonist radiotracer 11 C-(+)-PHNO

Fernando Caravaggio, Shinichiro Nakajima, Carol Borlido, Gary Remington, Philip Gerretsen, Alan Wilson, Sylvain Houle, Mahesh Menon, David Mamo, Ariel Graff-Guerrero

研究成果: Article査読

27 被引用数 (Scopus)

抄録

Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D 2/3 receptors (D 2/3 R) in humans in vivo. Our group has developed 11 C-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D 3 R. Thus, the use of 11 C-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D 2/3 R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D 3 R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a 11 C-(+)-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). 11 C-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D 2 R-rich regions (caudate and putamen), mixed D 2/3 R-rich regions (ventral striatum and globus pallidus), and extrastriatal D 3 R-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. 11 C-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D 2 R and D 3 R in neuropsychiatric populations.

本文言語English
ページ(範囲)2769-2776
ページ数8
ジャーナルNeuropsychopharmacology
39
12
DOI
出版ステータスPublished - 2014 11

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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