Effects of antidepressant drugs on the behavioral and physiological responses to lipopolysaccharide (LPS) in rodents

Raz Yirmiya*, Yehuda Pollak, Ohr Barak, Ronit Avitsur, Haim Ovadia, Michael Bette, Eberhard Weihe, Joseph Weidenfeld

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

205 Scopus citations


Antidepressants produce various immunomodulatory effects, as well as an attenuation of the behavioral responses to immune challenges, such as lipopolysaccharide (LPS). To explore further the effects of antidepressants on neuroimmune interactions, rats were treated daily with either fluoxetine (Prozac) or saline for 5 weeks, and various behavioral, neuroendocrine, and immune functions were measured following administration of either LPS or saline. Chronic fluoxetine treatment significantly attenuated the anorexia and body weight loss, as well as the depletion of CRH-41 from the median eminence and the elevation in serum corticosterone levels induced by LPS. Chronic treatment with imipramine also attenuated LPS-induced adrenocortical activation. In rats and in mice, which normally display a biphasic body temperature response to LPS (initial hypothermia followed by hyperthermia), chronic treatment with fluoxetine completely abolished the hypothermic response and facilitated and strengthened the hyperthermic response. The effects of antidepressants on the responsiveness to LPS are probably not mediated by their effects on peripheral proinflammatory cytokine production, because LPS-induced expression of TNFα and IL-1β mRNA in the spleen (assessed by semiquantitative in situ hybridization) was not altered following chronic treatment with either fluoxetine or imipramine. The effects of antidepressants on the acute phase response may have important clinical implications for the psychiatric and neuroendocrine disturbances that are commonly associated with various medical conditions.

Original languageAmerican English
Pages (from-to)531-544
Number of pages14
Issue number5
StatePublished - 2001

Bibliographical note

Funding Information:
The authors thank Edna Cohen, Roee Canaan, Inbal Goshen, and Anna Itzik for their help in running the experiments. This work was supported by Grant 94-204 from the United-States-Israel Binational Science Foundation, by a grant from the Milton Rosenbaum Foundation for Psychiatric Research, and by the Center for Research on Pain, The Hebrew University of Jerusalem. RY is a member of the Eric Roland Center for Neurodegenerative diseases.


  • Corticosterone
  • Corticotrophin-releasing hormone (CRH)
  • Depression
  • Fever
  • Fluoxetine (Prozac)
  • Imipramine
  • Interleukin-1β (IL-1β)
  • Lipopolysaccharide (LPS)
  • Tumor Necrosis Factor-α (TNFα)


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