Specific serotonin reuptake inhibitor-induced decreases in lymphocyte activity require endogenous serotonin release

Neuroimmunomodulation. 2000;8(4):179-87. doi: 10.1159/000054278.

Abstract

Objectives: We have previously reported that acute administration of the specific serotonin reuptake inhibitor (SSRI), fluoxetine, resulted in a decrease in mitogen-induced blood lymphocyte proliferation. The present studies further examine the specificity of this response to serotonin reuptake systems and the potential role of endogenous serotonin in mediating these effects.

Methods: Male Sprague-Dawley rats were treated intraperitoneally with the SSRIs, fluoxetine (6-10 mg/kg) or sertraline (20 mg/kg), dopamine and norepinephrine reuptake inhibitors, GBR 12909 and desipramine, respectively (6 mg/kg) or the serotonin precursor, 5-hydoxytryptophan (5-HTP, 50 mg/kg) 2 h prior to sacrifice. The serotonin-depleting agents, p-chlorophenylalanine (PCPA, 2 x 200 mg/kg) or the serotonin-lesioning agent, p-chloroamphetamine (PCA, 2 x 10 mg/kg) were administered intraperitoneally 5-7 days prior to fluoxetine (10 mg/kg) administration.

Results: Unlike the SSRIs, which significantly suppressed lymphocyte proliferation responses, selective norepinephrine or dopamine reuptake inhibition had no effect on lymphocyte proliferation. Elevation of extracellular serotonin levels with the serotonin precursor, 5-HTP, resulted in a similar decrease in lymphocyte proliferation as that seen with SSRI administration. Conversely, decreases in endogenous serotonin following PCA or PCPA treatment prevented the fluoxetine-induced decreases in lymphocyte proliferation.

Conclusions: These results suggest that decreases in mitogen-induced lymphocyte proliferation following acute fluoxetine administration were due to elevations in extracellular serotonin following reuptake inhibition.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5-Hydroxytryptophan / metabolism
  • 5-Hydroxytryptophan / pharmacology
  • Animals
  • Antidepressive Agents / pharmacology
  • Cell Division / drug effects
  • Desipramine / pharmacology
  • Dopamine Uptake Inhibitors / pharmacology
  • Fenclonine / pharmacology
  • Fluoxetine / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocytes / cytology
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Male
  • Mitogens / antagonists & inhibitors
  • Mitogens / pharmacology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Piperazines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin / metabolism*
  • Serotonin Antagonists / pharmacology
  • Sertraline / pharmacology
  • p-Chloroamphetamine / pharmacology

Substances

  • Antidepressive Agents
  • Dopamine Uptake Inhibitors
  • Mitogens
  • Piperazines
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Serotonin
  • p-Chloroamphetamine
  • vanoxerine
  • 5-Hydroxytryptophan
  • Sertraline
  • Fenclonine
  • Desipramine