Original Paper

Serotonin, 5-HT_1A Serotonin Receptors and Proliferation of Lymphocytes in Major Depression Patients
Alfonso González^b, Fili Fazzino^a, Mirta Castillo^b, Salvador Mata^b, Lucimey Lima<sup>a, b

a</sup>Laboratorio de Neuroquímica, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, and
^bServicio de Psiquiatría, Hospital Vargas de Caracas, Caracas, Venezuela

Address of Corresponding Author

Neuroimmunomodulation 2007;14:8-15 (DOI: 10.1159/000107283)

  Key Words

• Lymphocyte proliferation
• Major depression
• Serotonin 5-HT_1A receptor

  Abstract

Serotonin receptors are present in lymphocytes and might be related to the functionality of these cells in health and in pathology. The serotonergic system is affected in the brain and in peripheral immune cells of depressed patients. The objectives of this work were to evaluate the basal proliferation of lymphocytes, the response to the mitogen concanavalin A, and the role of serotonin 5-HT_1A receptors. Twenty-nine patients, 19-52 years old, were diagnosed for a major depression episode with the Statistical and Diagnostic Manual-IV of the American Psychiatric Association, approved by ethic committees and gave written consent. The Hamilton depression score was 30.60 ± 2.65. An apparently healthy group without a family history of psychiatric illness was included. Blood peripheral lymphocytes were isolated by density gradients with Ficoll/Hypaque and differential adhesion to plastic, cultured in 96-well plaques with RPMI-1640 medium with or without 4 µg/ml of concanavalin A. 8-Hydroxy-2-(di-n-propylamino)tetralin (5-40 nM) and WAY-100,478 (0.1-100 µM), agonist and antagonist of 5-HT_1A receptors, serotonin (12.5-100 nM) or imipramine (0.1-100 µM) were also added. Proliferation was evaluated at 72 h with 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide, and the optical density was 570 nm. Basal proliferation was three times higher in depressed patients than in controls, whereas no response to mitogen was obtained, and 5-HT_1A receptors significantly reacted to the agonist, with increases of about 31-54% at 10, 20 and 40 nM of the specific agonist, indicating initial activation probably in relation to autoimmunity and overreactivity of these receptors in depression. The antagonist reduced proliferation in mitogen-stimulated lymphocytes, 50% in controls and 70% in depressed patients, with a differential concentration dependency; probably, these receptors are more sensitive in depression due to increased 5-HT_1A receptor transduction. The antagonist also reduced the stimulation produced by the 5-HT_1A agonist. Imipramine caused biphasic effects according to concentrations, showing a possible dual role for serotonin, although all values were significantly higher in depressed subjects. The described alterations might be of relevance in the pathophysiology of depression.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Dr. Lucimey Lima
Laboratorio de Neuroquímica, Centro de Biofísica y Bioquímica
Instituto Venezolano de Investigaciones, Apdo. 21827
Caracas 1020-A (Venezuela)
Tel. +58 212 504 1213, Fax +58 212 504 1295, E-Mail llima@ivic.ve

  Article Information

Received: November 6, 2006
Accepted: January 23, 2007
Published online: August 15, 2007
Number of Print Pages : 8
Number of Figures : 4, Number of Tables : 0, Number of References : 55