Suppression of lipopolysaccharide-induced impairment of active avoidance and interleukin-6-induced increase of prostaglandin E2 release in rats by indometacin.
The effects of indometacin (CAS 53-86-1) on lipopolysaccharide-induced impairment of active avoidance and on interleukin-6-induced increase of prostaglandin E2 release were investigated in rats. In the experiment on acquisition and retention of one-way active avoidance in a shuttle box model, bilateral infusion of lipopolysaccharides (LPS) into the hippocampus, 1 microgram per side, resulted in a significant impairment both in acquisition and retention by prolonging the latency of avoidance in training and testing. In the meantime, intraperitoneal injection of indometacin 10 mg/kg daily for 7 days, improved the LPS-induced amnesia especially in the testing by shortening the latency from 2.3 to 1.7 s (p < 0.05). In the in vivo microdialysis study in anesthetized rats, intrahippocampal infusion of 80 ng interleukin-6 (IL-6) markedly increased prostaglandin E2 (PGE2) release into hippocampal dialysates which started at 2 h post administration. Perfusion of indometacin (0.3 mol/l) into the hippocampus for 1 h obviously suppressed the IL-6-induced PGE2 response. These findings provide experimental evidence that--assuming that central inflammation may be involved with Alzheimer's disease a non-steroidal anti-inflammatory drug may be used in the treatment of Alzheimer's disease.
Ma
T C
TC
Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Zhu
X Z
XZ
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D015232:Dinoprostone / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D017551:Microdialysis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D015850:Interleukin-6; D008070:Lipopolysaccharides; D015232:Dinoprostone; D007213:Indomethacin