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Lack of age-dependent decrease in dopamine D3 receptor availability: a [(11)C]-(+)-PHNO and [(11)C]-raclopride positron emission tomography study.
J Cereb Blood Flow Metab. 2015 Nov; 35(11):1812-8.JC

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+Show Affiliations

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.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.Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Centre for Addiction and Mental Health, Campbell Research Institute, Toronto, Ontario, Canada.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.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.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.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.Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Centre for Addiction and Mental Health, Campbell Research Institute, Toronto, Ontario, Canada.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.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26058690

Citation

Nakajima, Shinichiro, et al. "Lack of Age-dependent Decrease in Dopamine D3 Receptor Availability: a [(11)C]-(+)-PHNO and [(11)C]-raclopride Positron Emission Tomography Study." Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, vol. 35, no. 11, 2015, pp. 1812-8.
Nakajima S, Caravaggio F, Boileau I, et al. Lack of age-dependent decrease in dopamine D3 receptor availability: a [(11)C]-(+)-PHNO and [(11)C]-raclopride positron emission tomography study. J Cereb Blood Flow Metab. 2015;35(11):1812-8.
Nakajima, S., Caravaggio, F., Boileau, I., Chung, J. K., Plitman, E., Gerretsen, P., Wilson, A. A., Houle, S., Mamo, D. C., & Graff-Guerrero, A. (2015). Lack of age-dependent decrease in dopamine D3 receptor availability: a [(11)C]-(+)-PHNO and [(11)C]-raclopride positron emission tomography study. Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 35(11), 1812-8. https://doi.org/10.1038/jcbfm.2015.129
Nakajima S, et al. Lack of Age-dependent Decrease in Dopamine D3 Receptor Availability: a [(11)C]-(+)-PHNO and [(11)C]-raclopride Positron Emission Tomography Study. J Cereb Blood Flow Metab. 2015;35(11):1812-8. PubMed PMID: 26058690.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lack of age-dependent decrease in dopamine D3 receptor availability: a [(11)C]-(+)-PHNO and [(11)C]-raclopride positron emission tomography study. AU - Nakajima,Shinichiro, AU - Caravaggio,Fernando, AU - Boileau,Isabelle, AU - Chung,Jun K, AU - Plitman,Eric, AU - Gerretsen,Philip, AU - Wilson,Alan A, AU - Houle,Sylvain, AU - Mamo,David C, AU - Graff-Guerrero,Ariel, Y1 - 2015/06/10/ PY - 2014/10/27/received PY - 2015/03/17/revised PY - 2015/04/23/accepted PY - 2015/6/11/entrez PY - 2015/6/11/pubmed PY - 2016/2/18/medline SP - 1812 EP - 8 JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JO - J Cereb Blood Flow Metab VL - 35 IS - 11 N2 - 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. SN - 1559-7016 UR - https://www.unboundmedicine.com/medline/citation/26058690/Lack_of_age_dependent_decrease_in_dopamine_D3_receptor_availability:_a_[_11_C]__+__PHNO_and_[_11_C]_raclopride_positron_emission_tomography_study_ L2 - https://journals.sagepub.com/doi/10.1038/jcbfm.2015.129?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -