Lipopolysaccharide- and glutamate-induced hypothalamic hydroxyl radical elevation and fever can be suppressed by N-methyl-D-aspartate-receptor antagonists.
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| Abstract |
The purpose of the current study was to explore the effects of N-methyl-D-aspartate (NMDA)-receptor antagonists (MK-801 and LY235959) administered intracerebroventricularly on the changes of both core temperature and hypothalamic levels of 2,3-dihydroxybenzoic acid (2,3-DHBA) induced by intracerebroventricular injection of glutamate (100 - 400 microg at 10 microl/rabbit) or intravenous administration of lipopolysaccharide (LPS) (2 microg/kg) in rabbits. The measurements of 2,3-DHBA were used as an index of the intrahypothalamic levels of hydroxyl radicals. The rise in both the core temperature and hypothalamic 2,3-DHBA could be induced by intracerebroventricular injection of glutamate or intravenous administration of LPS. The glutamate- or LPS-induced fever and increased hypothalamic levels of 2,3-DHBA were significantly antagonized by pretreatment with injection of MK-801 or LY235959 1 h before glutamate or LPS injection. The increased levels of prostaglandin E2 in the hypothalamus induced by glutamate or LPS could be suppressed by MK-801 or LY235959. The data demonstrate that prior antagonism of NMDA receptors in the brain, in addition to reducing prostaglandin E2 production in the hypothalamus, suppresses both the glutamate- and LPS-induced fever and increased hypothalamic hydroxyl radicals.
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| Authors | Cheng-Hsing Kao, Ting-Yu Kao, Wu-Tein Huang, Mao-Tsun Lin |
| Journal | Journal of pharmacological sciences (J Pharmacol Sci) Vol. 104 Issue 2 Pg. 130-6 (Jun 2007) ISSN: 1347-8613 [Print] Japan |
| PMID | 17538230 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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