A role for endogenous histamine and its H-3 receptor subtype for media
ting drinking elicited by eating was examined in adult male Sprague-Da
wley rats. The IP injection of the H-3 agonist R-alpha-methylhistamine
(Ramh, 2.5 mg/kg) shortened the latency to initiate drinking and incr
eased 1-h water intake in nondeprived rats freely eating pellets and d
rinking water. The ICV injection (through a surgically implanted chron
ic cannula) of 10 mu g Ramh increased water intake; this Ramh-induced
drinking was abolished by previous ICV injection of the H-3 antagonist
thioperamide (Th, 60 mu g). For rats drinking and eating after 24-h f
ood deprivation, SC Th inhibited drinking behavior: for example, 10 mg
/kg Th SC delayed the latency to initiate drinking and inhibited 1-h w
ater intake without inhibition of food intake. In contrast, 60 mu g Th
ICV failed to inhibit food-related drinking in rats eating after food
deprivation. For nondeprived rats eating a small cracker, 10 mg/kg Th
SC delayed the latency to initiate drinking and abolished water intak
e without effect on eating, and 60 mu g Th ICV had similar effects upo
n drinking elicited by ingestion of cracker. The IG infusion (through
a surgically implanted gastric catheter) of 2 ml 600 or 900 mOsm/kg Na
Cl, a treatment that is subthreshold for increase in systemic plasma o
smolality at the initiation of drinking, elicited drinking that was ab
olished by 10 mg/kg Th SC and attenuated by 60 mu g Th ICV. The IG inf
usion of 2 ml 1800 mOsm/kg NaCl, a treatment that is above threshold f
or increase in systemic plasma osmolality, elicited drinking that was
attenuated by 10 mg/kg SC or 60 mu g Th ICV. These results demonstrate
that peripheral and central H-3 receptors for histamine have a role i
n drinking elicited by eating and the postprandial gastrointestinal os
motic consequences of eating. These findings extend the evidence demon
strating a histaminergic contribution to food-related drinking in rats
.