Role of hypothalamic histamine in stimulating the corticosterone release in rats

Intracerebroventricular injection of alpha-fluoromethylhistidine caused a significant decrease of the histamine content of the hypothalamus as well as of plasma adrenocorticotropic hormone and corticosterone concentrations. A high correlation was observed between the histamine content of the hypothalamus and the plasma corticosterone concentration. When the histamine content of the hypothalamus decreased, the plasma concentration of corticosterone diminished. Almost the same result was obtained when the posterior hypothalamus was lesioned electrically. The increases in plasma adrenocorticotropic hormone and corticosterone concentrations, induced by intracerebroventricular injection of histamine in sham-operated rats, were abolished after hypothalamic lesioning. When electrical stimulations were applied to the posterior hypothalamus, plasma adrenocorticotropic hormone and corticosterone concentrations increased significantly and, at the same time, evoked potentials were recorded on the adrenal nerve. An increase in plasma corticosterone concentration, induced by hypothalamic stimulation, was also observed even after hypophysectomy, suggesting that another corticosterone-secreting pathway exists apart from the hypophysis-adrenocortex system. The increase in plasma adrenocorticotropic hormone and corticosterone concentrations was inhibited not only by pyrilamine and cimetidine, but also by (R)-alpha-methyl-histamine, and H3 agonist. In addition, the effect of this latter product was inhibited by thioperamide, an H3 antagonist. These results indicate that hypothalamic histamine plays an important role in the stimulation of the corticosterone release in rats.