Behavioral and neurochemical consequences of lipopolysaccharide in mice: anxiogenic-like effects

Lacosta, Susan; Merali, Zul; Anisman, Hymie

doi:10.1016/s0006-8993(98)01288-8

Cited by 142 publications

(85 citation statements)

References 56 publications

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“…Experimentally these typically take the form of exteroceptive threats-those arising from the environment, notably potential predators in the form of predator scents, or of open spaces where predators may lurk. The findings from our studies, and those of others (Basso et al 2003;Castex, et al 1995;Lacosta et al 1999;Rossi-George et al 2005) indicate, however, that interoceptive threats, such as infection or allergy or systemic immune challenge, also can engage behaviors typical of threat avoidance, and increase drive on brain regions that process threat-related information. These areas also contribute to neurocircuitry that support stress responses.…”

Section: What May Be the Adaptive Value Of Enhanced Anxiety During Gucontrasting

confidence: 52%

Infection-induced viscerosensory signals from the gut enhance anxiety: Implications for psychoneuroimmunology

Goehler

Lyte

Gaykema

2007

Brain, Behavior, and Immunity

120

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Infection and inflammation lead to changes in mood and cognition. Although the "classic" sickness behavior syndrome, involving fatigue, social withdrawal, and loss of appetites are most familiar, other emotional responses accompany immune activation, including anxiety. Recent studies have shown that gastrointestinal bacterial infections lead to enhanced anxiety-like behavior in mice. The bacteria-induced signal is most likely carried by vagal sensory neurons, and occurs early on (within six hours) during the infection. These signals induce evidence of activation in brain regions that integrate viscerosensory information with mood, and potentiate activation in brain regions established as key players in fear and anxiety. The findings underline the importance of viscerosensory signals arising from the gastrointestinal tract in modulation of behaviors appropriate for coping with threats, and suggest that these signals may contribute to affective symptoms associated with gastrointestinal disorders.

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Section: What May Be the Adaptive Value Of Enhanced Anxiety During Gucontrasting

confidence: 52%

Infection-induced viscerosensory signals from the gut enhance anxiety: Implications for psychoneuroimmunology

Goehler

Lyte

Gaykema

2007

Brain, Behavior, and Immunity

120

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“…Instead, LPS induced an increased turnover of serotonin, as already described. 44,45 This alteration in serotoninergic neurotransmission was not responsible for the development of LPS-induced depressive-like behavior, since it was not blocked by 1-MT. It could be argued that such an effect was not detected, because we did not measure serotonin turnover in discrete brain areas.…”

Section: Discussionmentioning

confidence: 94%

Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice

O’Connor

Lawson²,

André³

et al. 2008

Mol Psychiatry

1,126

992

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Although elevated activity of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) has been proposed to mediate comorbid depression in inflammatory disorders, its causative role has never been tested. We report that peripheral administration of lipopolysaccharide (LPS) activates IDO and culminates in a distinct depressive-like behavioral syndrome, measured by increased duration of immobility in both the forced-swim and tail suspension tests. Blockade of IDO activation either indirectly with the anti-inflammatory tetracycline derivative minocycline, that attenuates LPS-induced expression of proinflammatory cytokines, or directly with the IDO antagonist 1-methyltryptophan (1-MT), prevents development of depressive-like behavior. Both minocycline and 1-MT normalize the kynurenine/tryptophan ratio in the plasma and brain of LPS-treated mice without changing the LPS-induced increase in turnover of brain serotonin. Administration of L-kynurenine, a metabolite of tryptophan that is generated by IDO, to naive mice dose dependently induces depressive-like behavior. These results implicate IDO as a critical molecular mediator of inflammation-induced depressive-like behavior, probably through the catabolism of tryptophan along the kynurenine pathway.

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“…In mice, low doses of LPS (1 μg/mouse ip) induced elevations of plasma ACTH and corticosterone, both of which reached peaks at around 2 h [26]. Increased concentrations of MHPG and MHPG:NE ratios also appeared throughout the brain with a similar time course [26,[140][141][142][143]. This response was greatest in the hypothalamus, suggesting a relatively greater activation of the VNAB compared to the DNAB.…”

Section: Neurochemical Responses To Endotoxin (Lps)mentioning

confidence: 99%

“…This response was greatest in the hypothalamus, suggesting a relatively greater activation of the VNAB compared to the DNAB. LPS also induces small increases of DOPAC in most brain regions, including prefrontal cortex, hypothalamus and brain stem [26,[140][141][142][143][144]. Peak responses in both DA and NE occurred around 2 h [26].…”

Section: Neurochemical Responses To Endotoxin (Lps)mentioning

confidence: 99%

Effects of cytokines and infections on brain neurochemistry

Dunn

2006

Clinical Neuroscience Research

285

169

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Administration of cytokines to animals can elicit many effects on the brain, particularly neuroendocrine and behavioral effects. Cytokine administration also alters neurotransmission, which may underlie these effects. The most well studied effect is the activation of the hypothalamopituitary-adrenocortical (HPA) axis, especially that by interleukin-1 (IL-1). Peripheral and central administration of IL-1 also induces norepinephrine (NE) release in the brain, most markedly in the hypothalamus. Small changes in brain dopamine (DA) are occasionally observed, but these effects are not regionally selective. IL-1 also increases brain concentrations of tryptophan, and the metabolism of serotonin (5-HT) throughout the brain in a regionally nonselective manner. Increases of tryptophan and 5-HT, but not NE, are also elicited by IL-6, which also activates the HPA axis, although it is much less potent in these respects than IL-1. IL-2 has modest effects on DA, NE and 5-HT. Like IL-6, tumor necrosis factor-α (TNFα) activates the HPA axis, but affects NE and tryptophan only at high doses. The interferons (IFN's) induce fever and HPA axis activation in man, but such effects are weak or absent in rodents. The reported effects of IFN's on brain catecholamines and serotonin have been very varied. However, interferon-γ, and to a lesser extent, interferon-α, have profound effects on the catabolism of tryptophan, effectively reducing its concentration in plasma, and may thus limit brain 5-HT synthesis.Administration of endotoxin (LPS) elicits responses similar to those of IL-1. Bacterial and viral infections induce HPA activation, and also increase brain NE and 5-HT metabolism and brain tryptophan. Typically, there is also behavioral depression. These effects are strikingly similar to those of IL-1, suggesting that IL-1 secretion, which accompanies many infections, may mediate these responses. Studies with IL-1 antagonists, support this possibility, although in most cases the antagonism is incomplete, suggesting the existence of multiple mechanisms. Because LPS is known to stimulate the secretion of IL-1, IL-6 and TNFα, it seems likely that these cytokines mediate at least some of the responses, but studies with antagonists indicate that there are multiple mechanisms. The neurochemical responses to cytokines are likely to underlie the endocrine and behavioral responses. The NE response to IL-1 appears to be instrumental in the HPA activation, but other mechanisms exist. Neither the noradrenergic nor the serotonergic systems appear to be involved in the major behavioral responses. The significance of the serotonin response is unknown.

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Behavioral and neurochemical consequences of lipopolysaccharide in mice: anxiogenic-like effects

Cited by 142 publications

References 56 publications

Infection-induced viscerosensory signals from the gut enhance anxiety: Implications for psychoneuroimmunology

Infection-induced viscerosensory signals from the gut enhance anxiety: Implications for psychoneuroimmunology

Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice

Effects of cytokines and infections on brain neurochemistry

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