The H₃ receptor is involved in cholecystokinin inhibition of food intake in rats

We investigated the peripheral effects of an H₃-receptor agonist and an H₃-receptor antagonist (R)α-methylhistamine (Rα-MeHA) and thioperamide, respectively, on basal feeding and the CCK8-induced inhibition of food intake in rat. Intraperitoneal injection of thioperamide reduced food intake in a dose-dependent manner with maximal inhibition (35%, P<0.01 vs saline) at 3 mg/kg. (R)α-MeHA (0.3-3 mg/kg i.p.), an H₃-receptor agonist alone had no effect on feeding but reversed the thioperamide-induced inhibition of food intake in a dose-dependent manner. The maximal feeding inhibitory dose of thioperamide (3 mg.kg i.p) increased by 40% and 22 % (P<0.01 vs saline) brain and stomach histamine contents, respectively. Histamine (0.3 - 6 mg/kg i.p.) and CCK-8 (3 - 30 μg/kg i.p) also inhibited food intake in a dose-dependent manner. Inhibition was 20% to 40% for histamine and 40% to 80% (P<0.01 vs saline) for CCK8. CCK-8 inhibition of feeding was increased by thioperamide and prevented by (R)α-MeHA in a dose-dependent way. In addition, CCK-8 did not reduce food intake if rats were pretreated with pyrilamine or ranitidine postsynaptic H₁- and H₂-receptor antagonists respectively. Our data suggest that the H₃-receptor is involved in basal feeding. They also suggest that CCK satiety depends upon the release of histamine which acts on the H₂- and H₁-receptors, the final mediators of this effect.