S. Hayley et al., Central monoamine and plasma corticosterone changes induced by a bacterialendotoxin: sensitization and cross-sensitization effects, EUR J NEURO, 13(6), 2001, pp. 1155-1165
Low doses of lipopolysaccharide, tumour necrosis factor-alpha (TNF-alpha),
interleukin-1 beta (IL-1 beta), or exposure to a stressor (restraint) incre
ased plasma corticosterone levels. In animals pretreated with lipopolysacch
aride, a marked sensitization of the corticosterone response was evident up
on subsequent exposure to lipopolysaccharide, TNF-alpha, or restraint, 1 da
y later. As well, the sickness-inducing effects of lipopolysaccharide, TNF-
alpha and IL-1 beta were markedly increased in mice pretreated with lipopol
ysaccharide. The sensitization effects were marked when the second treatmen
t was administered 1 day after lipopolysaccharide administration, but not w
hen a 28-day interval elapsed. In a second experiment, TNF-alpha influenced
monoamine functioning in the paraventricular nucleus of the hypothalamus a
nd within extrahypothalamic regions, including the central amygdala, locus
coeruleus, prefrontal cortex. Moreover, serotonin activity within the centr
al amygdala, as well as dopamine activity within the prefrontal cortex, wer
e subject to a sensitization effect in animals pretreated with lipopolysacc
haride 1 day earlier. Macrophage depletion by a suspension of clodronate li
posomes attenuated the plasma corticosterone changes induced by TNF-alpha,
but did not affect the sensitization. In contrast, the acute effects of TNF
-alpha on central neurotransmitters were unaffected by the liposome suspens
ion, but this treatment prevented the sensitization. These data may be rele
vant to clinical situations in which individuals exposed to bacterial infec
tions may be rendered more susceptible to the behavioural and neurochemical
effects of subsequently encountered stressors and immunological challenges
.