title: Lack of age-dependent decrease in dopamine D3 receptor availability: a [(11)C]-(+)-PHNO and [(11)C]-raclopride positron emission tomography study.
abstract: Positron emission tomography with antagonist radiotracers has showed that striatal dopamine D2/3 receptor (D2/3R) availability decreases with age. However, no study has specifically assessed whether D2/3R availability decreases with age in healthy persons as measured with agonist radiotracers. Moreover, it is unknown whether D3R availability changes with age in healthy humans. Thus, we explored the relationship between age and D2/3R availability in healthy humans using the D3 receptor (D3R)-preferential agonist radiotracer [(11)C]-(+)-PHNO (n=72, mean±s.d. age=40±15, range=18 to 73) and the antagonist [(11)C]-Raclopride (n=70, mean±s.d. age =40±14, range=18 to 73) (both, n=33). The contribution of D3R to the [(11)C]-(+)-PHNO signal varies across regions of interest; the substantia nigra and hypothalamus represent D3R-specific regions, the ventral pallidum, globus pallidus, and ventral striatum represent D2/3R-mixed regions, and the caudate and putamen represent D2 receptor (D2R)-specific regions. With [(11)C]-(+)-PHNO, a negative correlation was observed between age and nondisplaceable binding potential (BPND) in the caudate (r(70)=-0.32, P=0.005). No correlations were observed in the other regions. With [(11)C]-Raclopride, negative correlations were observed between age and BPND 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 D2R availability, these findings suggest that D3R availability does not change with age.
authors.affiliation: Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Caravaggio
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Centre for Addiction and Mental Health, Campbell Research Institute, Toronto, Ontario, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
authors.affiliation: Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jun K
authors.initials: JK
authors.lastname: Chung
authors.affiliation: Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Plitman
authors.affiliation: Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Gerretsen
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.|Centre for Addiction and Mental Health, Campbell Research Institute, Toronto, Ontario, Canada.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Centre for Addiction and Mental Health, Campbell Research Institute, Toronto, Ontario, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.affiliation: Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Department of Psychiatry, University of Malta, Valletta, Malta.
authors.forename: David C
authors.initials: DC
authors.lastname: Mamo
authors.affiliation: Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Centre for Addiction and Mental Health, Campbell Research Institute, Toronto, Ontario, Canada.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry / Q000502:physiology*; D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D005917:Globus Pallidus / Q000000981:diagnostic imaging / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D049268:Positron-Emission Tomography / Q000379:methods*; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D020891:Raclopride; D019275:Radiopharmaceuticals; D050637:Receptors, Dopamine D3 / Q000187:drug effects*; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D010078:Oxazines; D019275:Radiopharmaceuticals; D050637:Receptors, Dopamine D3; C042631:naxagolide; D020891:Raclopride