Nitric oxide synthase inhibition into the rat locus coeruleus delays the LPS‐induced fever

Abstract

This work was aimed at analyzing whether nitric oxide (NO) synthesis in the rat locus coeruleus (LC) is essential for mounting the LPS‐induced fever. Male Wistar rats (320–350g) were chronically, stereotaxically implanted with one guide cannula just above the LC and had a miniature temperature datalogger (SubCue) inserted in the peritoneal cavity. Unanesthetized, freely moving rats were unilaterally microinjected into the LC with either a nonselective nitric oxide synthase (NOS) inhibitor [L‐NMMA; 50 nmol in 100 nL of pyrogen‐free saline (PFS)] or just PFS as control, and were, 30 min later, intraperitoneally injected with either a polyphasic fever‐inducing dose of bacterial lipopolysaccharide [LPS; 100 μg/kg in PFS (1 mL/kg)] or PFS (vehicle), at an isothermal, subneutral ambient temperature (23°C). Under NOS inhibition, we observed an increased latency (1 h) for the onset of fever and also a mild, transient attenuation of its second phase (F2,18=5.334; p<0.001, vs control groups); a thermal index analysis showed a slighter fever (F2,18=5.482; p=0.0138, vs control groups). Moreover, measurements of LC nitrite/nitrate concentration revealed that the LC nitric oxide synthesis increased during the course of fever (p<0.001, vs saline group). These results indicate that the endogenous synthesis of NO into the rat LC mediates the onset of the LPS‐induced fever. Financial support: FAPESP, CNPq.