Altered expression of autonomic neurotransmitter receptors and proliferative responses in lymphocytes from a chronic mild stress model of depression: effects of fluoxetine

Brain Behav Immun. 2002 Aug;16(4):333-50. doi: 10.1006/brbi.2001.0632.

Abstract

We studied beta-adrenergic and muscarinic cholinergic receptor (MR) expression and proliferative response in lymphocytes from animals under chronic mild stress (CMS) model of depression (CMS animals). Animals were subjected to CMS (periods of food or water deprivation, changes in lighting conditions, tilted cage, etc.) for 12 weeks. CMS lymphocytes showed an altered mitogen-induced proliferation. CMS-B and -T lymphocytes showed an increment on beta-adrenoceptor number and on intracellular responses to a beta-agonist. CMS-T cells showed higher MR expression and lower cGMP responses than normal lymphocytes. MR were not detectable in normal B cells while CMS-B cells showed both MR expression and cGMP response. Beta and muscarinic stimulation influenced lymphocyte proliferative responses, in accordance with cAMP and cGMP responses. After 12 weeks of the CMS procedure, animals were treated with fluoxetine while the CMS procedure continued. Fluoxetine treatment reverted the alterations induced by CMS. These findings suggest a possible mechanism for the immune alterations found in depressive disorders and for the effect of fluoxetine treatment on immune response.

MeSH terms

  • Adrenergic beta-Antagonists / metabolism
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Antidepressive Agents, Second-Generation / pharmacology*
  • Autonomic Nervous System / drug effects
  • Autonomic Nervous System / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CD4-CD8 Ratio
  • Cell Division / drug effects
  • Cell Division / immunology
  • Chronic Disease
  • Cyclic AMP / metabolism
  • Cyclic GMP / metabolism
  • Disease Models, Animal
  • Female
  • Fluoxetine / pharmacology*
  • Iodine Radioisotopes
  • Mice
  • Mice, Inbred BALB C
  • Mitogens / pharmacology
  • Muscarinic Antagonists / metabolism
  • Muscarinic Antagonists / pharmacology
  • Pindolol / analogs & derivatives*
  • Pindolol / metabolism
  • Pindolol / pharmacology
  • Quinuclidinyl Benzilate / metabolism
  • Quinuclidinyl Benzilate / pharmacology
  • Radioligand Assay
  • Receptors, Adrenergic, beta / analysis
  • Receptors, Adrenergic, beta / biosynthesis*
  • Receptors, Muscarinic / analysis
  • Receptors, Muscarinic / biosynthesis*
  • Stress, Psychological / drug therapy*
  • Stress, Psychological / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tritium

Substances

  • Adrenergic beta-Antagonists
  • Antidepressive Agents, Second-Generation
  • Iodine Radioisotopes
  • Mitogens
  • Muscarinic Antagonists
  • Receptors, Adrenergic, beta
  • Receptors, Muscarinic
  • Fluoxetine
  • Tritium
  • cyanopindolol
  • Quinuclidinyl Benzilate
  • Pindolol
  • Cyclic AMP
  • Cyclic GMP