Cyclooxygenase 1 is not essential for hypophagic responses to interleukin-1 and endotoxin in mice

Numerous studies have shown that the effects of interleukin-1 (IL-1) and endotoxin (LPS) on behavior are sensitive to cyclooxygenase (COX) inhibitors. However, neither the location of the COX involved nor the specific isoform, COX1 or COX2, is known. A previous study using selective COX1 and COX2 inhibitors did not provide an unequivocal answer. Therefore, we tested the response of sweetened milk ingestion to IL-1 and LPS in mice in which the COX1 or the COX2 gene was deleted (COX1ko and COX2ko). When IL-1beta was administered 90 min before the milk, COX1ko mice showed responses similar to those of normal mice. In contrast, COX2ko mice exhibited responses considerably less than normal, with some mice showing no response. Indomethacin pretreatment almost prevented the feeding responses to IL-1 in normal and COX1ko mice. The milk intake response to LPS in COX1ko mice was like that of normal mice. The results from COX1ko mice suggest that COX1 is not necessary for the decreased milk intake following IL-1 and LPS. The results from COX2ko mice are consistent with the involvement of COX2 in the IL-1-induced depression of milk intake, but other mechanisms may effect decreases in sweetened milk intake.