title: 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.
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-HT2A receptor binding. Similarly, 8-week administration of the 5-HT2A/5-HT2C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, at a dose which down-regulates brain 5-HT2A/2C receptors, did not alter brain or platelet 5-HT transporters or platelet 5-HT2A 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-HT2A 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-HT2A 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.
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Owens
authors.forename: C A
authors.initials: CA
authors.lastname: Ballenger
authors.forename: D L
authors.initials: DL
authors.lastname: Knight
authors.forename: C B
authors.initials: CB
authors.lastname: Nemeroff
mesh_terms: D000662:Amphetamines / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D002352:Carrier Proteins / Q000378:metabolism*; D015283:Citalopram / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists / Q000378:metabolism*; D010133:p-Chloroamphetamine / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; C493232:Slc6a4 protein, rat; D015283:Citalopram; D012701:Serotonin; D010133:p-Chloroamphetamine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D003345:Corticosterone