Effects of Antidepressant Drugs on the Behavioral and Physiological Responses to Lipopolysaccharide (LPS) in Rodents

Abstract

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 TNFSeveral lines of evidence indicate that antidepressants produce various immunomodulatory effects. In depressed patients, the effects of antidepressants are variable and seem to be related to the immune status of the patients at the initiation of the treatment. When depression was associated with immune activation, antidepressants reduced immune function and cytokine secretion. For example, the increased plasma levels of IL-6 during acute depression were normalized by 8-week treatment with fluoxetine (Sluzewska et al. 1995), the increased monocyte counts in depressed patients were reduced following 6-weeks treatment with tricyclic antidepressants (TCAs) (Seidel et al. 1996), and the increased numbers of leukocytes and neutrophils were also reduced by antidepressant treatment (Maes et al. 24 , NO . 5 1997). On the other hand, when immune functions were found to be normal, antidepressants had no immunological effects; for example, chronic moclobemide treatment had no effect on monocytes functions, TNF ␣ production or IFN ␥ levels (Landmann et al. 1997). Moreover, in a study of depressed patients who exhibited immune suppression before treatment, the TCA clomipramine increased the production of IL-1 ␤ , IL-2, and IL-3 (Weizman et al. 1994).In experimental animals, TCAs as well as selective serotonin reuptake inhibitors (SSRIs) produce mainly immune suppression and anti-inflammatory effects. For example, antidepressant treatment in vivo inhibited the increased acute phase response in olfactory bulbectomized rats, a useful animal model of depression (Song and Leonard 1994), reduced the production of interleukin-1 (IL-1) and IL-2 in a chronic mild stress model of depression (Kubera et al. 1996), inhibited immune activation in rats with experimental allergic neuritis (Zhu et al. 1994), and produced anti-inflammatory ...

Effects of Centrally Administered Etanercept on Behavior, Microglia, and Astrocytes in Mice Following a Peripheral Immune Challenge

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Multiple antidepressant potential modes of action of curcumin: a review of its anti-inflammatory, monoaminergic, antioxidant, immune-modulating and neuroprotective effects

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