Role of centrally administered melatonin and inhibitors of COX and NOS in LPS-induced hyperthermia and adipsia

in the present study we have examined the effect of centrally administered non-steroidal antiinflammatory drugs (NSAIDS), nitric oxide synthase (NOS) inhibitor and melatonin on lipopolysaccharide (LPS)induced hyperthermia and its anti-dipsogenic effect. Intracerebroventricular (i.c.v.) administratio n of LPS (100-200 ng/rat) induces a dose dependent elevation in body temper ature and decreases water consumption in 24 h water deprived rats. Coadmini stration of NSAIDS (indomethacin and nimesulide: 10 nM/rat each) with LPS ( 100 ng) reversed, whereas NOS inhibitor N-G-nitro-L-arginine methyl ester ( L-NAME: 10-20 mu g/rat) enhanced LPS-induced hyperthermia. In contrast L-NA ME reversed the LPS-induced anti-dipsogenic effect in a dose dependent mann er, whereas NSAIDS showed no change in the effect of LPS. Further, centrall y administered prostaglandin E-2 (PGE(2), 0.5-1 mu g/rat) produced hyperthe rmia without affecting the drinking behavior, suggesting that two independe nt mechanisms operate in LPS-induced hyperthermia and in the anti-dipsogeni c effect. The pineal hormone melatonin is known to inhibit cellular damage caused by LPS, produced dose dependent (5-10 nM.icv) inhibition of LPS-indu ced hyperthermia and adipsia, but failed to reverse the PGE(2)-induced hype rthermia, shows reversal of LPS-induced hyperthermia by melatonin is due to inhibition of prostaglandin synthesis rather than antagonism of prostaglan din action. The overall study reveals that inhibition of both NO and prosta glandin production by melatonin might be responsible for its reversal of LP S-induced hyperthermia and adipsia.