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

Antidepressants produce various immunomodulatory effects, as well as an att enuation of the behavioral responses to immune challenges, such as lipopoly saccharide (LPS). To explore further the effects of antidepressants on neur oimmune interactions, rats were treated daily with either fluoxetine (Proza c) or saline for 5 weeks, and various behavioral, neuroendocrine, and immun e functions were measured following administration of either LPS or saline. Chronic fluoxetine treatment significantly attenuated tire anorexia and bo dy weight loss, ns well as the depletion oi CXH-41 from tile median eminenc e and the elevation in serum corticosterone levels induced by LPS. Chronic treatment with imipramine also attenuated LPS-induced adrenocortical activa tion. In vats and in mice, which normally display a biphasic body temperatu re response to LPS (initial hypothermia followed by hyperthermia), chronic treatment with fluoxetine completely abolished tile hypothermic response an d facilitated and strengthened the hyperthermic response. The effects of an tidepressants on the responsiveness to LPS are probably not mediated by the ir effects on peripheral proinflammatory cytokine production, because LPS-i nduced expression of TNF alpha and IL-1 beta mRNA in the spleen (assessed b y semiquantitative in situ hybridization) was not altered following chronic treatment with either fluoxetine or imipramine. The effects of antidepress ants on the acute phase response may have important clinical implications f or the psychiatric and neuroendocrine disturbances that are commonly associ ated with various medical conditions. (C) 2001 American College of Neuropsy chopharmacology. Published by Elsevier Science Inc.