Effects of intracerebroventricularly infused histamine and selective H1, H2 and H3 agonists on food and water intake and urine flow in Wistar rats

The actions of intracerebroventricularly infused histamine and selective histamine H-1, H-2 and H-3 receptor agonists on food and water intake and urine flow were studied in rats. It was found that 100-800 nmoles of histamine significantly suppressed feeding. The H-1 agonist 2-(3-trifluoromethylphenyl)histamine (FMPH) decreased food intake, whereas the H-2 agonist dimaprit was without effect. Histamine- and FMPH-induced suppressions of feeding were attenuated by blockade of H-1 but not by H-2 receptors. The results clearly demonstrate that activation of brain H-1 receptors decreases food intake. In subsequent studies, we found that both metoprine and thioperamide, which increase histaminergic activity through different mechanisms, also reduced food intake. This finding indicates that the brain histaminergic system is associated with feeding behavior. The same is true with body water homeostasis. Histamine caused a long-lasting diuresis. Also dimaprit and metoprine increased urine flow and the blockade of H-2 receptors abolished the diuretic responses to histamine and dimaprit. On the other hand, the H-3 agonist (R)-alpha-methylhistamine elicited drinking and this effect could be prevented by thioperamide pretreatment. The results imply that activation of H-3 receptors predominantly provokes drinking, whereas central H-2 receptors mediate the diuretic effect of histamine. (C) 1998 Elsevier Science B.V. All rights reserved.