Central monoamine and plasma corticosterone changes induced by a bacterial endotoxin: Sensitization and cross-sensitization effects

Shawn Hayley, Susan Lacosta, Zul Merali, Nico Van Rooijen, Hymie Anisman

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54 Citations (Scopus)


Low doses of lipopolysaccharide, tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), or exposure to a stressor (restraint) increased plasma corticosterone levels. In animals pretreated with lipopolysaccharide, a marked sensitization of the corticosterone response was evident upon subsequent exposure to lipopolysaccharide, TNF-α, or restraint, 1 day later. As well, the sickness-inducing effects of lipopolysaccharide, TNF-α and IL-1β were markedly increased in mice pretreated with lipopolysaccharide. The sensitization effects were marked when the second treatment was administered 1 day after lipopolysaccharide administration, but not when a 28-day interval elapsed. In a second experiment, TNF-α influenced monoamine functioning in the paraventricular nucleus of the hypothalamus and within extrahypothalamic regions, including the central amygdala, locus coeruleus, prefrontal cortex. Moreover, serotonin activity within the central amygdala, as well as dopamine activity within the prefrontal cortex, were subject to a sensitization effect in animals pretreated with lipopolysaccharide 1 day earlier. Macrophage depletion by a suspension of clodronate liposomes attenuated the plasma corticosterone changes induced by TNF-α, but did not affect the sensitization. In contrast, the acute effects of TNF-α on central neurotransmitters were unaffected by the liposome suspension, but this treatment prevented the sensitization. These data may be relevant to clinical situations in which individuals exposed to bacterial infections may be rendered more susceptible to the behavioural and neurochemical effects of subsequently encountered stressors and immunological challenges.

Original languageEnglish
Pages (from-to)1155-1165
Number of pages11
JournalEuropean Journal of Neuroscience
Issue number6
Publication statusPublished - 2001
Externally publishedYes


  • Lipopolysaccharide
  • Mouse
  • Neurotransmitter
  • Sickness
  • TNF-α


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