Platelet 5-hydroxytryptamine (5-HT) transporter and 5-HT2A 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

Michael J. Owens, Cynthia A. Ballenger, David L. Knight, Charles B. Nemeroff

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

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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