MEDIATION BY NITRIC-OXIDE FORMATION IN THE PREOPTIC AREA OF ENDOTOXINAND TUMOR NECROSIS FACTOR-INDUCED INHIBITION OF WATER-INTAKE IN THE RAT

1 Drinking was induced in rats by 24 h of water deprivation. Water int ake (ml) was evaluated for a 1 h period. 2 N(G)-nitro-L-arginine methy l ester (L-NAME, 5-10 mug, i.c.v., 50-100 ng into the preoptic area (P OA)), an inhibitor of nitric oxide (NO) synthase, and methylene blue ( 50 - 100 ng into POA), an inhibitor of guanylate cyclase activation, a ntagonized the inhibition of drinking induced by E. coli endotoxin (LP S, 640 mug kg-1, i.v.) and tumour necrosis factor (TNFalpha, 40 ng, i. c.v.) in 24 h water-deprived rats. 3 L-Arginine (25, 50 and 100 ng), t he precursor aminoacid of NO, but not the stereoisomer D-arginine (100 ng), inhibited drinking induced by water deprivation when injected in to 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 e xhibit antidipsogenic effects. 4 TNFalpha (20 and 40 ng, i.c.v.; 1.25, 2.5 and 5 ng into the POA) showed a dose-dependent and powerful inhib ition 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 1 0 ng of TNFalpha given i.c.v. had no effect on the intake of water. 5 LPS and TNFalpha, given at doses (160 mug 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 trea ted with a dose of L-arginine (12.5 ng, into the POA) which did not mo dify drinking by itself. (LPS + L-arginine: 53.6% of inhibition; TNFal pha + L-arginine: 52.0% of inhibition). 6 These results suggest that N O into the POA: (1) acts as an inhibitory mechanism on thirst and (2) plays a role in the antidipsogenic effect of LPS and TNFalpha.