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

doi:10.1016/0006-8993(90)91672-4

Brain Research

Volume 528, Issue 2, 1 October 1990, Pages 308-310

https://doi.org/10.1016/0006-8993(90)91672-4 Get rights and content

Abstract

Dopaminergic pathways to the cerebral cortex may be involved in cognitive function. We examined the effect of aging on the D₁ dopamine receptors, and their high-agonist affinity (RH) sites, in postmortem human frontal cortex (n = 32; age range, 19–88 years). With aging, there was a significant decrease in the densities of the D₁ dopamine receptors, and their RH sites, in human frontal cortex. The age-related reduction of cortical dopaminergic neurotransmission might contribute to the decline in cognitive abilities of elderly persons.

References (19)

De KeyserJ. et al.
Evidence for a widespread dopaminergic innervation of the human cerebral neocortex
Neurosci. Lett.
(1989)
De KeyserJ. et al.
Autoradiographic localization of the D₁ and D₂ dopamine receptors in human brain
Neurosci. Lett.
(1988)
De KeyserJ. et al.
D₁ dopamine receptors in human putamen, frontal cortex and calf retina: differences in guanine nucleotide regulation of agonist binding and adenylate cyclase stimulation
Brain Research
(1988)
DescarriesL. et al.
Regional and laminar density of the dopamine innervation in adult rat cerebral cortex
Neuroscience
(1987)
Le MoalM. et al.
Radiofrequency lesion of the ventral mesencephalic tegmentum: neurological and behavioral considerations
Exp. Neurol.
(1976)
LowryO.H. et al.
Protein measurement with the Folin phenol reagent
J. Biol. Chem.
(1951)
RinneJ.O.
Muscarinic and dopaminergic receptors in the aging human brain
Brain Research
(1987)
ScattonB. et al.
Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson's disease
Brain Research
(1983)
AdolfssonR. et al.
Postmortem distribution of dopamine and homovanillic acid in human brain, variations related to age and a review of the literature
J. Neural. Transm.
(1979)

There are more references available in the full text version of this article.

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

Abstract

Neurosci. Lett.

Neurosci. Lett.

Brain Research

Neuroscience

Exp. Neurol.

J. Biol. Chem.

Brain Research

Brain Research

Postmortem distribution of dopamine and homovanillic acid in human brain, variations related to age and a review of the literature

J. Neural. Transm.

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