SUPPRESSION OF LIPOPOLYSACCHARIDE-INDUCED IMPAIRMENT OF ACTIVE-AVOIDANCE AND INTERLEUKIN-6-INDUCED INCREASE OF PROSTAGLANDIN E-2 RELEASE INRATS BY INDOMETHACIN

The effects of indometacin (CAS 53-86-1) on lipopolysaccharide-induced impairment of active avoidance and on interleukin-6-induced increase of prostaglandin E-2 release were investigated in rats. In the experim ent on acquisition and retention of one-way active avoidance in a shut tle box model, bilateral infusion of lipopolysaccharides (LPS) into th e hippocampus, 1 mu g per side, resulted in a significant impairment b oth in acquisition and retention by prolonging the latency of avoidanc e in training and testing. In the meantime, intraperitoneal injection of indometacin 10 mg/kg daily for 7 days, improved the LPS-induced amn esia 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 ra ts, intrahippocampal infusion of 80 ng interleukin-6 (IL-6) markedly i ncreased prostaglandin E-2(PGE(2)) 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-i nduced PGE(2) response. These findings provide experimental evidence t hat - assuming that central inflammation may be involved with Alzheime r's disease a non-steroidal anti-inflammatory drug may be used in the treatment of Alzheimer's disease.