Lipopolysaccharide- and Glutamate-Induced Hypothalamic Hydroxyl Radical Elevation and Fever Can Be Suppressed by N-Methyl-D-aspartate-Receptor Antagonists

• Published in: Journal of Pharmacological Sciences 2007, Vol.104(2), pp.130-136
• Main Authors: Kao, Cheng-Hsing, Kao, Ting-Yu, Huang, Wu-Tein, Lin, Mao-Tsun
• Format: Article
• Language: English
• Subjects: Animals; Dinoprostone - biosynthesis; Dizocilpine Maleate - administration & dosage; Dizocilpine Maleate - pharmacology; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - pharmacology; fever; Fever - chemically induced; Fever - drug therapy; Glutamic Acid; Hydroxybenzoates - metabolism; hydroxyl radical; Hydroxyl Radical - metabolism; hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Injections, Intraventricular; Isoquinolines - administration & dosage; Isoquinolines - pharmacology; Lipopolysaccharides; Male; N-methyl- D -aspartate (NMDA) receptor; prostaglandin; Rabbits; Random Allocation; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.FP0070272

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 µg at 10 µl/rabbit) or intravenous administration of lipopolysaccharide (LPS) (2 µg/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.