CACABELOS, R., YAMATODANI, A., FUKUI, H., NIIGAWA, H., MIYAKE, A., WATANABE, T., NISHIMURA, T. and WADA, H. Time- and Dose-Dependent Responses of Brain Histamine to Intracerebroventricular and Intraperitoneal Administrations of Growth Hormone-Releasing Factor (GRF_1-44). Tohoku J. exp. Med., 1987, 151 (4), 429-442 - Changes in the level of histamine (HA) in rat brain induced by intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administrations of growth hormone-releasing factor (GRF_1-44) were studied. HA was determined by high-performance liquid chromatography (HPLC) in the anterior hypothalamic region, posterior hypothalamic region, median eminence, adenohypophysis, neurohypophysis, hippocampus and prefrontal cortex. GRF_1-44 (1-10μg, i.c.v.) induced significant time- and dose-dependent increases in the concentration of HA in the hypothalamo-hypophyseal system and time-dependent decrease of HA in the hippocampus. In contrast, after i.p. administration of GRF_1-44 (10μg) the level of HA in the hypothalamus tended to decrease but the total amount of H-1 receptors in the hypothalamo-hypophyseal system did not change. Circadian variations in the GRF-induced HA and growth hormone responses were also observed, responses being lower in the evening than in the morning. It is concluded that GRF interacts with HA at the central level to optimize the function of the somatotropinergic system.