Histamine plays a major role for drinking elicited by spontaneous eating in rats.

The effects of combined antagonism of H1 (using 1 mg/kg dexbrompheniramine IP) and H2 (using 16 mg/kg cimetidine IP) receptors for histamine prior to (a) drinking after 2.5 mg/kg histamine SC, (b) drinking after 1-hr water deprivation, and (c) drinking during spontaneous eating were examined at 1 hr into the dark phase of a 12:12'-hr light/dark cycle for 14 Sprague-Dawley male rats. Such antagonism of histamine receptors abolished drinking elicited by exogenous histamine without affecting drinking after water deprivation. Histaminergic antagonism did not affect spontaneous eating, but it appeared to abolish drinking prior to a meal (for only those 3 rats which exhibited such drinking), delayed the latency to initiate drinking after initiating a meal, and inhibited drinking which occurred during and after eating but prior to postprandial resting (i.e., satiety for food). Because antagonism of peripheral histamine receptors inhibited food-related drinking by over 60%, these results provide indirect support for the hypothesis that the preabsorptive food-contingent vagally-mediated release of gastric mucosal histamine plays a major role in spontaneous food-related drinking in the rat.