Mediation by nitric oxide formation in the preoptic area of endotoxin and tumour necrosis factor‐induced inhibition of water intake in the rat

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Abstract
Drinking was induced in rats by 24 h of water deprivation. Water intake (ml) was evaluated for a 1 h period. NG‐nitro‐l‐arginine methyl ester (l‐NAME, 5–10 μg, i.c.v., 50–100 ng into the preoptic area (POA)), an inhibitor of nitric oxide (NO) synthase, and methylene blue (50–100 ng into POA), an inhibitor of guanylate cyclase activation, antagonized the inhibition of drinking induced by E. coli endotoxin (LPS, 640 μg kg−1, i.v.) and tumour necrosis factor (TNFα, 40 ng, i.c.v.) in 24 h water‐deprived rats. l‐Arginine (25, 50 and 100 ng), the precursor aminoacid of NO, but not the stereoisomer d‐arginine (100 ng), inhibited drinking induced by water deprivation when injected into the POA 30 min before water presentation (74.4% of inhibition with the highest dose). A dose of 12.5 ng l‐arginine into the POA did not exhibit antidipsogenic effects. TNFα (20 and 40 ng, i.c.v.; 1.25, 2.5 and 5 ng into the POA) showed a dose‐dependent and powerful inhibition of drinking behaviour in water‐deprived rats (70.4% and 80.8%, i.c.v. and into POA, with the highest doses, respectively). A dose of 10 ng of TNFα given i.c.v. had no effect on the intake of water. LPS and TNFα, given at doses (160 μg kg−1, i.v. and 10 ng, i.c.v., respectively) that did not influence drinking in water‐deprived rats, exhibited a strong antidipsogenic effect in water‐deprived rats treated with a dose of l‐arginine (12.5 ng, into the POA) which did not modify drinking by itself. (LPS + l‐arginine: 53.6% of inhibition; TNFα + l‐arginine: 52.0% of inhibition). These results suggest that NO into the POA: (1) acts as an inhibitory mechanism on thirst and (2) plays a role in the antidipsogenic effect of LPS and TNFα.