Pavlovian conditioning of endotoxin-tolerance in rats.
The most fascinating example of the bi-directional interaction between the central nervous system (CNS) and immune system is the behavioral conditioning of immune functions. We therefore investigated the behavioral conditioning of lipopolysaccharide (LPS)-induced endotoxin tolerance using the taste aversion paradigm. The conditioned stimulus (CS) saccharin was paired with the unconditioned stimulus (UCS) LPS over a five (CONDl) or four (COND2) days learning trial. Controls received drinking water with (SHAM) or without (UNT) LPS. Endotoxin tolerance was tested by determination of LPS-induced tumor necrosis factor (TNF)-alpha release. After the avoidance of the induced endotoxin-tolerance the CS saccharin was re-presented in all experimental groups. A the end of the re-exposure period a complete endotoxin tolerance was noticed in the CONDl- and COND2-group. In contrast, no effect of saccharin administration was observed in the SHAM- or UNT-group. Our data demonstrate for the first time the behavioral conditioning of endotoxin tolerance. Furthermore, these results contribute new aspects to the mechanisms underlying the development and modulation of endotoxin tolerance.
Oberbeck
Reiner
R
Department of Trauma Surgery, University Hospital of Essen, Hufelandstr 55 45122 Essen, Germany. reineroberbeck@hotmail.com
Kromm
Alexander
A
Exton
Michael S
MS
Schade
Ullrich
U
Schedlowski
Manfred
M
D000818:Animals; D001362:Avoidance Learning; D003214:Conditioning, Classical / Q000502:physiology*; D004361:Drug Tolerance / Q000502:physiology; D004731:Endotoxins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012439:Saccharin / Q000494:pharmacology; D013649:Taste / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D012439:Saccharin