Central nitric oxide synthase inhibition restores behaviorally mediated lipopolysaccharide induced fever in near-term rats

It has recently been established that the febrile response to bacterial endotoxin attenuated late in pregnancy is partially restored by central inhibition of nitric oxide synthase (NOS). To determine if this restoration of the febrile response also extends to warm-seeking behavior, we used a thermocline to allow animals to select their preferred ambient temperature. Near-term pregnant (day 19-20) and aged matched non-pregnant rats were given an I.P. injection of lipopolysaccharicle (LIPS, 50 mu g/kg) and an intracerebroventricular (I.C.V.) injection of an inhibitor of NOS, N-G-monomethyl-L-arginine acetate salt (L-NMMA, 100 mu g) or vehicle. Core body temperature and self-selected ambient temperature were measured for 6 h after injection. Inhibition of brain NOS before LPS injection resulted in a significant febrile response with an associated increase in selected ambient temperature in both near-term and non-pregnant animals. As expected, near-term dams that received I.C.V. vehicle+I.P. LPS did not have a febrile response but displayed a small hypothermic reaction with no change in selected ambient temperature. We conclude that blockade of brain NOS restores maternal hyperthermic and warm-seeking responses to LPS in near-term pregnancy. (c) 2008 Elsevier Inc. All rights reserved.