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Age-related changes in binding of the D2/3 receptor radioligand [11C](+)PHNO in healthy volunteers
- Source :
- NeuroImage. 130:241-247
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Objective Previous imaging studies with positron emission tomography (PET) have reliably demonstrated an age-associated decline in the dopamine system. Most of these studies have focused on the densities of dopamine receptor subtypes D 2/3 R (D 2 R family) in the striatum using antagonist radiotracers that are largely nonselective for D 2 R vs. D 3 R subtypes. Therefore, less is known about any possible age effects in D 3 -rich extrastriatal areas such as the substantia nigra/ventral tegmental area (SN/VTA) and hypothalamus. This study sought to investigate whether the receptor availability measured with [ 11 C](+)PHNO, a D 3 R-preferring agonist radiotracer, also declines with age. Methods Forty-two healthy control subjects (9 females, 33 males; age range 19–55 years) were scanned with [ 11 C](+)PHNO using a High Resolution Research Tomograph (HRRT). Parametric images were computed using the simplified reference tissue model (SRTM2) with cerebellum as the reference region. Binding potentials ( BP ND ) were calculated for the amygdala, caudate, hypothalamus, pallidum, putamen, SN/VTA, thalamus, and ventral striatum and then confirmed at the voxel level with whole-brain parametric images. Results Regional [ 11 C](+)PHNO BP ND displayed a negative correlation between receptor availability and age in the caudate ( r = − 0.56, corrected p = 0.0008) and putamen ( r = − 0.45, corrected p = 0.02) in healthy subjects (respectively 8% and 5% lower per decade). No significant correlations with age were found between age and other regions (including the hypothalamus and SN/VTA). Secondary whole-brain voxel-wise analysis confirmed these ROI findings of negative associations and further identified a positive correlation in midbrain (SN/VTA) regions. Conclusion In accordance with previous studies, the striatum (an area rich in D 2 R) is associated with age-related declines of the dopamine system. We did not initially find evidence of changes with age in the SN/VTA and hypothalamus, areas previously found to have a predominantly D 3 R signal as measured with [ 11 C](+)PHNO. A secondary analysis did find a significant positive correlation in midbrain (SN/VTA) regions, indicating that there may be differential effects of aging, whereby D 2 R receptor availability decreases with age while D 3 R availability stays unchanged or is increased.
- Subjects :
- Adult
Male
0301 basic medicine
Agonist
Aging
medicine.medical_specialty
medicine.drug_class
Cognitive Neuroscience
Striatum
Article
Young Adult
03 medical and health sciences
0302 clinical medicine
Dopamine
Internal medicine
Image Interpretation, Computer-Assisted
medicine
Radioligand
Humans
Carbon Radioisotopes
Receptors, Dopamine D2
Chemistry
business.industry
Putamen
Ventral striatum
Receptors, Dopamine D3
Brain
Middle Aged
Healthy Volunteers
Ventral tegmental area
030104 developmental biology
Endocrinology
medicine.anatomical_structure
nervous system
Neurology
Dopamine receptor
Positron-Emission Tomography
Dopamine Antagonists
Female
Radiopharmaceuticals
Nuclear medicine
business
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 10538119
- Volume :
- 130
- Database :
- OpenAIRE
- Journal :
- NeuroImage
- Accession number :
- edsair.doi.dedup.....1629902d16c2b26c877ab01a4fa1fe1b