Autoradiographic analysis of serotonin 5-HT1A receptor binding in the human brain postmortem: effects of age and alcohol

doi:10.1016/0006-8993(91)90171-Q

Brain Research

Volume 554, Issues 1–2, 19 July 1991, Pages 56-64

https://doi.org/10.1016/0006-8993(91)90171-Q Get rights and content

Quantitative autoradiographic analysis of serotonin 5-HT_1A receptors in the human brain, using [³H]8-OH-DPAT as a ligand, reveals region-specific decreases in receptor labeling with age in several cortical and hippocampal regions and in the raphe nuclei. This is due to a change in receptor density(B_max) with no apparent change in affinity(K_d) as affirmed by saturation binding analysis on representative cortical regions. The presence of alcohol is associated with decreased binding in several cortical gyri. Suicide, gender and postmortem delay had no effect on 8-OH-DPAT binding.

References (35)

BiegonA. et al.
Characterization and localization of serotonin receptors in human brain postmortem
Brain Research
(1986)
BradleyP.B. et al.
Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine
Neuropharmacology
(1986)
CrowT.J. et al.
Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides
Neuropharmacology
(1984)
Gross-IsseroffR. et al.
Autoradiographic analysis of age-dependent changes in serotonin 5-HT2 receptors in the human brain postmortem
Brain Research
(1990)
HoyerD. et al.
Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-H1A recognition sites. Apparent absence of 5-HT1B recognition sites
Brain Research
(1986)
KoideT. et al.
Influence of a chronic new antidepressant, 1-[3-(dimethylamino)propyl]-5-methyl-3-phenyl-1H-indazole (FS32) and itsn-desmethylated compound (FS97) treatment on monoaminergic receptor sensitivity in the rat brain
Neuropharmacology
(1981)
McKeithI.G. et al.
5-HT receptor binding in post-mortem brain from patients with affective disorder
J. Affective Disorders
(1987)
MorganD.G.
The dopamine and serotonin systems during aging in human and rodent brain. A brief review
Prog. Neuropsychopharmacol. Biol. Psychiatr.
(1987)
MunsonP.J. et al.
LIGAND: a versatile computerized approach for characterization of ligand-binding systems
Anal. Biochem.
(1980)
OwenF. et al.
Serotonergic mechanisms in brains of suicide victims
Brain Research
(1986)

PazosA. et al.

Serotonin receptors in the human brain — III. Autoradiographic mapping of serotonin-1 receptors

Neuroscience

(1987)

SignsS.A. et al.

The role of dopamine and serotonin receptors in the mediation of the ethanol interoceptive cue

Pharmacol. Biochem. Behav.

(1988)

BlumK. et al.

Allelic association of human dopamine receptor gene in alcoholism

J. Am. Med. Assoc.

(1990)

CarlssonA. et al.

Biogenic amines in human brain in normal aging, senile dementia and chronic alcoholism

CarpenterM.B.

Human Neuroanatomy

(1976)

CrossA.J. et al.

High affinity serotonin binding sites in human brain: a comparison of cerebral cortex and basal ganglia

J. Neural Transm.

(1989)

DeArmondS.J. et al.

Structure of the Human Brain: A Photographic Atlas

(1974)

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Autoradiographic analysis of serotonin 5-HT1A receptor binding in the human brain postmortem: effects of age and alcohol

Brain Research

Neuropharmacology

Neuropharmacology

Brain Research

Brain Research

Neuropharmacology

J. Affective Disorders

Prog. Neuropsychopharmacol. Biol. Psychiatr.

Anal. Biochem.

Brain Research

Neuroscience

Pharmacol. Biochem. Behav.

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Autoradiographic analysis of serotonin 5-HT_1A receptor binding in the human brain postmortem: effects of age and alcohol