Lack of age-dependent decrease in dopamine D 3 receptor availability

A [11C]-(+)-PHNO and [11C]-raclopride positron emission tomography study

Shinichiro Nakajima, Fernando Caravaggio, Isabelle Boileau, Jun K. Chung, Eric Plitman, Philip Gerretsen, Alan A. Wilson, Sylvain Houle, David C. Mamo, Ariel Graff-Guerrero

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Positron emission tomography with antagonist radiotracers has showed that striatal dopamine D 2/3 receptor (D 2/3 R) availability decreases with age. However, no study has specifically assessed whether D 2/3 R availability decreases with age in healthy persons as measured with agonist radiotracers. Moreover, it is unknown whether D 3 R availability changes with age in healthy humans. Thus, we explored the relationship between age and D 2/3 R availability in healthy humans using the D 3 receptor (D 3 R)-preferential agonist radiotracer [11C]-(+)-PHNO (n=72, mean±s.d. age=40±15, range=18 to 73) and the antagonist [11C]-Raclopride (n=70, mean±s.d. age =40±14, range=18 to 73) (both, n=33). The contribution of D 3 R to the [11C]-(+)-PHNO signal varies across regions of interest; the substantia nigra and hypothalamus represent D 3 R-specific regions, the ventral pallidum, globus pallidus, and ventral striatum represent D 2/3 R-mixed regions, and the caudate and putamen represent D 2 receptor (D 2 R)-specific regions. With [11C]-(+)-PHNO, a negative correlation was observed between age and nondisplaceable binding potential (BP ND) in the caudate (r(70)=-0.32, P=0.005). No correlations were observed in the other regions. With [11C]-Raclopride, negative correlations were observed between age and BP ND in the caudate (r(68)=-0.50, P<0.001), putamen (r(68)=-0.41, P<0.001), and ventral striatum (r(68)=-0.43, P<0.001). In conclusion, in contrast with the age-dependent decrease in D 2 R availability, these findings suggest that D 3 R availability does not change with age.

Original languageEnglish
Pages (from-to)1812-1818
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume35
Issue number11
DOIs
Publication statusPublished - 2015 Jan 1

Fingerprint

Raclopride
Positron-Emission Tomography
Dopamine
Putamen
Corpus Striatum
Globus Pallidus
Substantia Nigra
Hypothalamus
naxagolide
Ventral Striatum

Keywords

  • aging
  • D receptor
  • D receptor
  • dopamine
  • positron emission tomography
  • [C]-(+)-PHNO
  • [C]-Raclopride

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Lack of age-dependent decrease in dopamine D 3 receptor availability : A [11C]-(+)-PHNO and [11C]-raclopride positron emission tomography study. / Nakajima, Shinichiro; Caravaggio, Fernando; Boileau, Isabelle; Chung, Jun K.; Plitman, Eric; Gerretsen, Philip; Wilson, Alan A.; Houle, Sylvain; Mamo, David C.; Graff-Guerrero, Ariel.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 35, No. 11, 01.01.2015, p. 1812-1818.

Research output: Contribution to journalArticle

Nakajima, S, Caravaggio, F, Boileau, I, Chung, JK, Plitman, E, Gerretsen, P, Wilson, AA, Houle, S, Mamo, DC & Graff-Guerrero, A 2015, 'Lack of age-dependent decrease in dopamine D 3 receptor availability: A [11C]-(+)-PHNO and [11C]-raclopride positron emission tomography study', Journal of Cerebral Blood Flow and Metabolism, vol. 35, no. 11, pp. 1812-1818. https://doi.org/10.1038/jcbfm.2015.129
Nakajima, Shinichiro ; Caravaggio, Fernando ; Boileau, Isabelle ; Chung, Jun K. ; Plitman, Eric ; Gerretsen, Philip ; Wilson, Alan A. ; Houle, Sylvain ; Mamo, David C. ; Graff-Guerrero, Ariel. / Lack of age-dependent decrease in dopamine D 3 receptor availability : A [11C]-(+)-PHNO and [11C]-raclopride positron emission tomography study. In: Journal of Cerebral Blood Flow and Metabolism. 2015 ; Vol. 35, No. 11. pp. 1812-1818.
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abstract = "Positron emission tomography with antagonist radiotracers has showed that striatal dopamine D 2/3 receptor (D 2/3 R) availability decreases with age. However, no study has specifically assessed whether D 2/3 R availability decreases with age in healthy persons as measured with agonist radiotracers. Moreover, it is unknown whether D 3 R availability changes with age in healthy humans. Thus, we explored the relationship between age and D 2/3 R availability in healthy humans using the D 3 receptor (D 3 R)-preferential agonist radiotracer [11C]-(+)-PHNO (n=72, mean±s.d. age=40±15, range=18 to 73) and the antagonist [11C]-Raclopride (n=70, mean±s.d. age =40±14, range=18 to 73) (both, n=33). The contribution of D 3 R to the [11C]-(+)-PHNO signal varies across regions of interest; the substantia nigra and hypothalamus represent D 3 R-specific regions, the ventral pallidum, globus pallidus, and ventral striatum represent D 2/3 R-mixed regions, and the caudate and putamen represent D 2 receptor (D 2 R)-specific regions. With [11C]-(+)-PHNO, a negative correlation was observed between age and nondisplaceable binding potential (BP ND) in the caudate (r(70)=-0.32, P=0.005). No correlations were observed in the other regions. With [11C]-Raclopride, negative correlations were observed between age and BP ND in the caudate (r(68)=-0.50, P<0.001), putamen (r(68)=-0.41, P<0.001), and ventral striatum (r(68)=-0.43, P<0.001). In conclusion, in contrast with the age-dependent decrease in D 2 R availability, these findings suggest that D 3 R availability does not change with age.",
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AU - Chung, Jun K.

AU - Plitman, Eric

AU - Gerretsen, Philip

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