Age-related reduction in dopamine D1 receptors in the human brain: from late childhood to adulthood, a positron emission tomography study

doi:10.1016/j.neuroscience.2010.01.034

Neuroscience

Volume 167, Issue 1, 28 April 2010, Pages 104-110

https://doi.org/10.1016/j.neuroscience.2010.01.034 Get rights and content

Abstract

Age-dependent decrease in dopamine receptor density throughout adulthood is well described, meanwhile less is known about development of dopamine system in humans and in vivo it has not been investigated. We examined dopamine D1 receptor (D1DR) binding in the cerebral cortex and striatum of 12 adolescents (mean age 13.5±1.8 years) and 18 young adults (25±2.3 years) using positron emission tomography (PET) and radioligand [¹¹C]SCH23390. Over the age span of 10–30 years [¹¹C]SCH23390 binding (binding potential, BP) declined in all brain regions. The rate of BP decline was age-segment and brain region dependent. Most pronounced decline in BP was observed in the cortical regions during adolescence (mean BP in adults lower by 14–26% as compared to adolescents, P<0.0001). Significantly slower rate of decline in BP was observed in two cortical regions (orbitofrontal and posterior cingulate cortices) and striatal regions. The present PET-study provides new evidence on the development of D1DR in humans in vivo which is of critical importance for understanding of the biology of neurodevelopmental disorders.

Section snippets

Subjects

The study was approved by the Research Ethics and the Radiation Safety Committees of the Karolinska University Hospital, Solna, Sweden. Participation in the study was voluntary and the subjects agreed to participate after receiving written and oral information. Written informed consent was obtained from the subjects and/or their parents in accordance with the Declaration of Helsinki. The study was carried out at the PET Centre, Department of Clinical Neuroscience, Karolinska Institutet.

The

Results

In the present cross-sectional study regional BPs were calculated for [¹¹C]SCH23390 binding to D1DR in 24 brain regions (including both hemispheres) of 30 subjects. The relationship between age and BP in representative cortical and striatal regions is visualized in Fig. 1. [¹¹C]SCH23390 binding to the D1DR declined in all cortical and striatal regions over the investigated age span (10–30 years). There was no asymmetry in radioligand binding for any region. Subsequent analyses were done on

Discussion

To our knowledge, this is the first examination of the age effect on a neurotransmission biomarker in vivo during adolescence. In adults, age-related decline in D1DR density has been reported in the post-mortem brain (de Kayser et al., 1990) and in PET studies in vivo (Suhara et al., 1991, Wang et al., 1998), with the rate of decline being in the range of 4–9% per decade. In the present PET-study on D1DR binding we found an overall age dependent decline of the BPs also in adolescence.

The age

Conclusion

The study results suggest that D1DR binding declines in a non-linear mode during transition from adolescence to adulthood. Decline in cortical D1DR BP was age segment-dependent, with most pronounced BP decline during adolescence. In addition, D1DR BP decline was brain region-specific: rates of BP reduction varied between brain regions about 10-fold, from highest in the frontal, occipital cortices and lowest in the ventral striatum. The present PET-study illustrates the importance of

Acknowledgments

The authors thank members of the Stockholm PET group for technical assistance, in particular Kjerstin Lind, Johan Mohlin for contribution in data collection. The study was supported by grants from the Swedish Research Council (Project 05925 and 09114). JA was sponsored by the Sällskapet Barnavård Foundation.

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Clinical NeuroscienceResearch PaperAge-related reduction in dopamine D1 receptors in the human brain: from late childhood to adulthood, a positron emission tomography study

Abstract

Section snippets

Subjects

Results

Discussion

Conclusion

Acknowledgments

Neuroimage

Brain Res

Neuroimage

Prev Med

Neuroscience

J Psychiatry Res

Brain Res

J Adolesc Health

J Rad Appl Instrum A

Eur J Pharmacol

Brain Res Dev Brain Res

Neuroscience

Brain Res

Neuropsychopharmacology

Brain Res

Neuroscience

Int J Dev Neurosci

Brain Res Dev Brain Res

Brain Cogn

Neuroscience

Brain Res Dev Brain Res

Neurobiol Aging

Prefrontal dopamine D1 receptors and working memory in schizophrenia

J Neurosci

Head fixation device for reproducible position alignment in transmission CT and positron emission tomography

J Comput Assist Tomogr

SCH 23390: the first selective dopamine D1-like receptor antagonist

CNS Drug Rev

A role for N-methyl-d-aspartate receptors in the regulation of synaptogenesis and expression of the polysialylated form of the neural cell adhesion molecule in the developing striatum

Dev Neurosci

Boot: bootstrap R (S-Plus) functions

R package, version 1

A PET study of D(1)-like dopamine receptor ligand binding during altered endogenous dopamine levels in the primate brain

Psychopharmacology (Berl)

The effect of aging on the D1 dopamine receptors in human frontal cortex

Brain Res

PET analysis of human dopamine receptor subtypes using 11C-SCH 23390 and 11C-raclopride

Psychopharmacology (Berl)

Reduced striatal D1 receptor binding in autosomal dominant nocturnal frontal lobe epilepsy

Neurology

Clinical Neuroscience
Research Paper
Age-related reduction in dopamine D1 receptors in the human brain: from late childhood to adulthood, a positron emission tomography study