Repeated lipopolysaccharide administration produces tolerance to anorexia and fever but not to inhibition of thirst in rat

In 24 h water and food deprived rats, a single lipopolysaccharide treatment (0.25, 0.50 and 1 mg/kg, i.p.) induced inhibition of thirst and hunger as well as fever. Moreover, the same treatment increased serum cytokines, plas ma nitrite/nitrate and corticosterone and urinary prostaglandin levels. In another group of 24 h water and food deprived rats, a repeated lipopolysacc haride treatment (0.25, 0.50 and 1 mg/kg, i.p.), given at 0, 2, 6, 12 and 2 4 h, induced tolerance to inhibition of food intake and fever, but not to a ntidipsogenic effect. Moreover, the same repeated treatment stopped the inc rease in serum cytokines, plasma corticosterone and urinary prostaglandin c oncentrations and failed to reduce plasma nitrite/nitrate levels. This data , together with the evidence that a pretreatment with N-G-nitro-L-arginine methyl ester hydrochloride (L-NAME) (5 and 10 mug per rat) reverses the ant idipsogenic effects in lipopolysaccharide tolerant rats, suggests that the persistent reduction of water intake after a repeated lipopolysaccharide tr eatment is due to the antidipsogenic action of nitric oxide in the brain. ( C) 2000 Published by Elsevier Science Ltd. on behalf of International Socie ty for Immunopharmacology. All rights reserved.