Relationship between histamine receptors in the brain and diazepam-induced hyperphagia in rats

We investigated whether histaminergic neurons in the brain are involved in diazepam-induced hyperphagia in rats. Pretreatment with intracerebroventricular (ICV) injection of either histamine H1-receptor antagonist, pyrilamine (10 and 30 micrograms) or histamine H2-receptor antagonist, famotidine (3 and 10 micrograms) did not affect only diazepam (1 mg/kg, subcutaneous, SC)-induced hyperphagia in nondeprived rats, but also spontaneous feeding in food-deprived rats. In addition, pretreatment with ICV injection of histamine H3-receptor antagonist, thioperamide, and histamine H3-receptor agonist, (R) alpha methylhistamine, enhanced and inhibited diazepam-induced hyperphagia (1 mg/kg, SC) in nondeprived rats, respectively. However, thioperamide and (R) alpha methylhistamine did not affect spontaneous feeding in food-deprived rats. These findings suggest that histaminergic neurons are not directly involved in diazepam-induced hyperphagia in rats. Furthermore, enhancement or inhibition of diazepam-induced hyperphagia by histamine H3-receptor antagonist or agonist may occur via histamine H3-receptors localized in the other neurons in the rat brain.