A role for cyclooxygenase-2 in lipopolysaccharide-induced anorexia in rats

1 Institute of Animal Sciences, Physiology, and Animal Husbandry, Swiss Federal Institute of Technology, 8603 Schwerzenbach, Switzerland; 2 Department of Psychiatry, Weill Medical College of Cornell University, Bourne Lab, White Plains, New York 10463; and 3 Johnson & Johnson Pharmaceutical Research & Development, Spring House, Pennsylvania 19477 Because nonselective cycloooxygenase (COX) inhibition attenuated anorexia after lipopolysaccharide (LPS) administration, we tested the ability of resveratrol (2.5, 10, and 40 mg/kg) and NS-398 (2.5, 10, and 40 mg/kg), selective inhibitors of the two COX isoforms COX-1 and -2, respectively, to attenuate LPS (100 µg/kg ip)-induced anorexia. NS-398 (10 and 40 mg/kg) administered with LPS at lights out attenuated LPS-induced anorexia, whereas resveratrol at all doses tested did not. Because prostaglandin (PG) E 2 is considered the major metabolite synthesized by COX, we measured plasma and cerebrospinal fluid (CSF) PGE 2 levels after LPS administration. LPS induced a time-dependent increase of PGE 2 in CSF but not in plasma. NS-398 (5, 10, and 40 mg/kg) blocked the LPS-induced increase in CSF PGE 2 , whereas resveratrol (10 mg/kg) did not. These results support a role of COX-2 in mediating the anorectic response to peripheral LPS and point at PGE 2 as a potential neuromodulator involved in this response. NS-398; resveratrol; prostaglandin E 2 ; food intake; fever