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Journal of Neuroscience, Vol 15, 2920-2934, Copyright © 1995 by Society for Neuroscience
Effect of bacterial endotoxin and interleukin-1 beta on hippocampal serotonergic neurotransmission, behavioral activity, and free corticosterone levels: an in vivo microdialysis study
AC Linthorst, C Flachskamm, P Muller-Preuss, F Holsboer and JM Reul
Max Planck Institute of Psychiatry, Department of Neuroendocrinology, Munich, Germany.
In this study the effect of immune system stimulation and
intracerebroventricular (i.c.v.) administration of interleukin-1 beta (IL-1
beta) on hippocampal serotonergic neurotransmission, behavioral activity,
and the hypothalamic-pituitary-adrenocortical (HPA) axis is described. An
in vivo microdialysis method was used to measure hippocampal extracellular
concentrations of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic
acid (5-HIAA) in conscious, freely moving rats. In addition, we established
a method to continuously monitor free corticosterone levels in dialysates.
Behavioral activity was scored by measuring the time during which rats were
active (locomotion, grooming, eating, drinking). We found a significant,
positive relationship between behavioral activity and hippocampal
extracellular concentrations of 5-HT. Intraperitoneal (i.p.) administration
of the bacterial endotoxin lipopolysaccharide (LPS; 30, 100, and 300
micrograms/kg body weight) produced an increase in the extracellular
concentrations of 5-HT and 5-HIAA in the hippocampus, which was paralleled
by a significant decline in behavioral activity and a marked increase in
extracellular corticosterone levels. Thus, the close correlation between
hippocampal extracellular 5-HT levels and behavioral activity observed in
control rats was disrupted in the LPS- treated animals. The effects of i.p.
LPS could be mimicked by i.c.v. application of recombinant human IL-1 beta
(hIL-1 beta; 100 ng). i.c.v. pretreatment with the IL-1 receptor antagonist
(IL-1ra; 10 micrograms) antagonized the hIL-1 beta-induced effects. IL-1ra
showed no intrinsic effects. Furthermore, it was found that i.c.v.
pretreatment with IL-1ra (10 micrograms) significantly attenuated the i.p.
LPS-induced (100 micrograms/kg body weight) rise in hippocampal
extracellular 5-HT levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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