Platelet 5-hydroxytryptamine (5-HT) transporter and 5-HT(2A) receptor binding after chronic hypercorticosteronemia, (±)-1-(2,5-dimethoxy-4- iodophenyl)-2-aminopropane administration or neurotoxin-induced depletion of central nervous system 5-HT in the rat

M. J. Owens, C. A. Ballenger, D. L. Knight, Charles Nemeroff

Research output: Contribution to journalArticle

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Abstract

There is considerable evidence that the number of platelet 5- hydroxytryptamine (5-HT) transporter binding sites, as measured by [3H]imipramine binding, are significantly decreased, and platelet 5-HT2 receptor density is increased, in drug-free patients with major depression. To investigate whether these changes in the platelet 5-HT transporter or 5- HT2 receptor sites resulted from known or hypothesized biochemical changes observed in major depression, we examined, in the rat, whether a chronic hyperglucocorticoid state, or decreases or increases in central nervous system 5-HT neurotransmission, altered binding of the selective ligands [3H]citalopram and [125I](±)-1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane to platelet and brain 5-HT transporters and 5-HT2 receptors, respectively. Chronic (6 weeks) hypercorticosteronemia did not alter either brain or platelet 5-HT transporter or 5-HT(2A) receptor binding. Similarly, 8-week administration of the 5-HT(2A)/5-HT(2C) agonist (±)-1-(2,5- dimethoxy-4-iodophenyl)-2-aminopropane, at a dose which down-regulates brain 5-HT(2A/2C) receptors, did not alter brain or platelet 5-HT transporters or platelet 5-HT(2A) receptors. Additionally, para-chloroamphetamine- (11 weeks) or fenfluramine-induced chronic (1.5-10 weeks) depletion of central nervous system 5-HT did not alter platelet 5-HT transporter or 5-HT(2A) receptor binding. Finally, there was no correlation between the number of 5-HT transporters in brain and platelets in any of the control or treatment groups. These findings suggest that the observed changes in platelet 5-HT transporter and 5-HT(2A) receptor binding in depressed patients are more apt to be of genetic origin (i.e., trait-dependent) rather than an epiphenomenon of hypercortisolemia or altered central nervous system 5-HT status.

Original languageEnglish
Pages (from-to)1040-1049
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume278
Issue number3
StatePublished - Dec 1 1996
Externally publishedYes

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Serotonin Receptors
Neurotoxins
Serotonin
Blood Platelets
Central Nervous System
Brain
4-iodo-2,5-dimethoxyphenylisopropylamine
p-Chloroamphetamine
Fenfluramine
Serotonin Receptor Agonists
Citalopram
Imipramine
Platelet Count
Synaptic Transmission
Down-Regulation
Binding Sites

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{f30276605a824c0b9c8cf7992cad4658,
title = "Platelet 5-hydroxytryptamine (5-HT) transporter and 5-HT(2A) receptor binding after chronic hypercorticosteronemia, (±)-1-(2,5-dimethoxy-4- iodophenyl)-2-aminopropane administration or neurotoxin-induced depletion of central nervous system 5-HT in the rat",
abstract = "There is considerable evidence that the number of platelet 5- hydroxytryptamine (5-HT) transporter binding sites, as measured by [3H]imipramine binding, are significantly decreased, and platelet 5-HT2 receptor density is increased, in drug-free patients with major depression. To investigate whether these changes in the platelet 5-HT transporter or 5- HT2 receptor sites resulted from known or hypothesized biochemical changes observed in major depression, we examined, in the rat, whether a chronic hyperglucocorticoid state, or decreases or increases in central nervous system 5-HT neurotransmission, altered binding of the selective ligands [3H]citalopram and [125I](±)-1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane to platelet and brain 5-HT transporters and 5-HT2 receptors, respectively. Chronic (6 weeks) hypercorticosteronemia did not alter either brain or platelet 5-HT transporter or 5-HT(2A) receptor binding. Similarly, 8-week administration of the 5-HT(2A)/5-HT(2C) agonist (±)-1-(2,5- dimethoxy-4-iodophenyl)-2-aminopropane, at a dose which down-regulates brain 5-HT(2A/2C) receptors, did not alter brain or platelet 5-HT transporters or platelet 5-HT(2A) receptors. Additionally, para-chloroamphetamine- (11 weeks) or fenfluramine-induced chronic (1.5-10 weeks) depletion of central nervous system 5-HT did not alter platelet 5-HT transporter or 5-HT(2A) receptor binding. Finally, there was no correlation between the number of 5-HT transporters in brain and platelets in any of the control or treatment groups. These findings suggest that the observed changes in platelet 5-HT transporter and 5-HT(2A) receptor binding in depressed patients are more apt to be of genetic origin (i.e., trait-dependent) rather than an epiphenomenon of hypercortisolemia or altered central nervous system 5-HT status.",
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T1 - Platelet 5-hydroxytryptamine (5-HT) transporter and 5-HT(2A) receptor binding after chronic hypercorticosteronemia, (±)-1-(2,5-dimethoxy-4- iodophenyl)-2-aminopropane administration or neurotoxin-induced depletion of central nervous system 5-HT in the rat

AU - Owens, M. J.

AU - Ballenger, C. A.

AU - Knight, D. L.

AU - Nemeroff, Charles

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N2 - There is considerable evidence that the number of platelet 5- hydroxytryptamine (5-HT) transporter binding sites, as measured by [3H]imipramine binding, are significantly decreased, and platelet 5-HT2 receptor density is increased, in drug-free patients with major depression. To investigate whether these changes in the platelet 5-HT transporter or 5- HT2 receptor sites resulted from known or hypothesized biochemical changes observed in major depression, we examined, in the rat, whether a chronic hyperglucocorticoid state, or decreases or increases in central nervous system 5-HT neurotransmission, altered binding of the selective ligands [3H]citalopram and [125I](±)-1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane to platelet and brain 5-HT transporters and 5-HT2 receptors, respectively. Chronic (6 weeks) hypercorticosteronemia did not alter either brain or platelet 5-HT transporter or 5-HT(2A) receptor binding. Similarly, 8-week administration of the 5-HT(2A)/5-HT(2C) agonist (±)-1-(2,5- dimethoxy-4-iodophenyl)-2-aminopropane, at a dose which down-regulates brain 5-HT(2A/2C) receptors, did not alter brain or platelet 5-HT transporters or platelet 5-HT(2A) receptors. Additionally, para-chloroamphetamine- (11 weeks) or fenfluramine-induced chronic (1.5-10 weeks) depletion of central nervous system 5-HT did not alter platelet 5-HT transporter or 5-HT(2A) receptor binding. Finally, there was no correlation between the number of 5-HT transporters in brain and platelets in any of the control or treatment groups. These findings suggest that the observed changes in platelet 5-HT transporter and 5-HT(2A) receptor binding in depressed patients are more apt to be of genetic origin (i.e., trait-dependent) rather than an epiphenomenon of hypercortisolemia or altered central nervous system 5-HT status.

AB - There is considerable evidence that the number of platelet 5- hydroxytryptamine (5-HT) transporter binding sites, as measured by [3H]imipramine binding, are significantly decreased, and platelet 5-HT2 receptor density is increased, in drug-free patients with major depression. To investigate whether these changes in the platelet 5-HT transporter or 5- HT2 receptor sites resulted from known or hypothesized biochemical changes observed in major depression, we examined, in the rat, whether a chronic hyperglucocorticoid state, or decreases or increases in central nervous system 5-HT neurotransmission, altered binding of the selective ligands [3H]citalopram and [125I](±)-1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane to platelet and brain 5-HT transporters and 5-HT2 receptors, respectively. Chronic (6 weeks) hypercorticosteronemia did not alter either brain or platelet 5-HT transporter or 5-HT(2A) receptor binding. Similarly, 8-week administration of the 5-HT(2A)/5-HT(2C) agonist (±)-1-(2,5- dimethoxy-4-iodophenyl)-2-aminopropane, at a dose which down-regulates brain 5-HT(2A/2C) receptors, did not alter brain or platelet 5-HT transporters or platelet 5-HT(2A) receptors. Additionally, para-chloroamphetamine- (11 weeks) or fenfluramine-induced chronic (1.5-10 weeks) depletion of central nervous system 5-HT did not alter platelet 5-HT transporter or 5-HT(2A) receptor binding. Finally, there was no correlation between the number of 5-HT transporters in brain and platelets in any of the control or treatment groups. These findings suggest that the observed changes in platelet 5-HT transporter and 5-HT(2A) receptor binding in depressed patients are more apt to be of genetic origin (i.e., trait-dependent) rather than an epiphenomenon of hypercortisolemia or altered central nervous system 5-HT status.

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