Pergamon 0031-9384(95)02048-Z Physiology & Behavior, Vol. 58, No. 6, 1091-1097, 1995 Copyright © 1995 Elsevier Science Inc. Printed in the USA. All rights reserved 0031-9384/95 $9.50 + .00 Histamine n 3 Receptors Contribute to Drinking Elicited by Eating in Rats F. SCOTr KRALY, 1 ROBERT A. TRIBUZIO, YOUNG-MEE KIM, MELISSA E. KEEFE AND JARED FINKELL Department of Psychology, Colgate University, Hamilton, NY 13346 USA Received 9 February 1995 KRALY, F. S., R. A. TRIBUZIO, Y.-M. KIM, M. E. KEEFE AND J. FINKELL. Histamine Hs receptors contribute to drinking elicited by eating in rats. FHYSIOL BEHAV 58(6) 1091-1097, 1995.--A role for endogenous histamine and its H a receptor subtype for mediating drinking elicited by eating was examined in adult male Sprague-Dawley rats. The IP injection of the H 3 agonist R-a-methylhistamine (Ramh, 2.5 mg/kg) shortened the latency to initiate drinking and increased 1-h water intake in nondeprived rats freely eating pellets and drinking water. The ICV injection (through a surgically implanted chronic calmula) of 10/~g Ramh increased water intake; this Ramh-induced drinking was abolished by previous ICV injection of the H 3 antagonist thioperamide (Th, 60/.~g). For rats drinking and eating after 24-h food deprivation, SC Th inhibited drinking behavior: for example, 10 mg/kg Th SC delayed the latency to initiate drinking and inhibited 1-h water intake without inhibition of food intake. In contrast, 60/.~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 intake without effect on eating, and 60 /~g Th ICV had similar effects upon drinking elicited by ingestion of cracker. The IG infusion (through a surgically implanted gastric catheter) of 2 ml 600 or 900 mOsm/kg NaCI, a treatment that is subthreshold for increase in systemic plasma osmolality at the initiation of drinking, elicited drinking that was abolished by 10 mg/kg Th SC and attenuated by 60 /~g Th ICV. The IG infusion of 2 ml 1800 mOsm/kg NaCI, a treatment that is above threshold for increase in systemic plasma osmolality, elicited drinking that was attenuated by 10 mg/kg SC or 60 /zg Th ICV. These results demonstrate that peripheral and central H 3 receptors for histamine have a role in drinking elicited by eating and the postprandial gastrointestinal osmotic consequences of eating. These findings extend the evidence demonstrating a histaminergic contribution to food-related drinking in rats. Histamine Thioperamide Histaminergic Drinking Food-related drinking H 3 receptors Ingestive behavior R-cz-Methylhistamine THE histamine H a receptor agonist R-a-methylhistamine (Ramh) elicits drinking in rats when injected systemically (6). Such Ramh-induced drinking can be abolished by the H 3 antagonist thioperamide (Th) but not by H 1 or H 2 receptor antagonist drugs given systemically (6). Because systemically injected Ramh and Th have access to H 3 receptors in the brain (3), these findings suggest that at least par: of exogenous histamine's dipsogenic properties are due to its ability to activate the H 3 receptor subtype in the periphery and/or in the brain. The involvement of peripheral H 1 and H 2 receptors in mediat- ing the dipsogenic properties of exogenous histamine is well known (15). It is also known that pharmacological blockade of peripheral (15), but not central (16), H 1 and H 2 receptors inhibits drinking elicited by eating: in a variety of experimental paradigms, demonstrating a role for peripheral endogenous histamine and H 1 and H 2 receptor subtypes in the type of drinking behavior that accounts for the majority of daily fluid intake in mammals-- food-related drinking. Blockade of H 1 and H 2 receptors using systemic injections of selective antagonist drugs inhibits drinking elicited by meals sufficient to cause postprandial hypovolemia and increases in systemic plasma osmolality (12) and drinking elicited by eating in the apparent absence of postprandial changes in systemic fluid balance (13,14). The recent development of drugs purported to act as selective agonists and antagonists for H a receptors for histamine (3,25) enables study of a role for H a histamine receptors and endoge- nous histamine for drinking elicited by eating. We studied (a) the ability of IP or ICV injections of the H 3 agonist Ramh to elicit drinking; (b) the ability of SC or ICV injections of the H 3 antagonist Th to inhibit drinking elicited by meals (eating pel- 1 To whom requests for reprints should be addressed. 1091