1 The circadian activity of the hypothalamic-pituitary-adrenal (HPA) axis is regulated by caloric ow in rats. During the dark cycle, it has been shown that, in fasted rats, the time-course pro®le of plasma concentrations of adrenocorticotropin (ACTH) and corticosterone parallels the pro®le of food intake in ad libitum fed animals. 2 Cholecystokinin (CCK) is involved in regulating food intake in rodents. CCK-8 reduces food intake by acting on CCK-A receptors subtype. 3 This work aims at establishing an eventual relationship between the modulatory role of CCK on food intake and its eect on HPA axis activity during fasting. 4 We studied the eect of CCK-A and CCK-B receptor antagonists on food intake during the ®rst period of the dark cycle. Under these conditions we observed that the CCK-A receptor antagonist, SR-27897 (0.3 mg kg 71), but not the CCK-B receptor antagonist, L-365260 (1 mg kg 71 ), increases food-intake. 5 In a second series of experiments we observed that the increase of both ACTH and corticosterone plasma level elicited by fasting, was prevented by SR-27897, but not by L-365260. 6 These results indicate that CCK-A receptor blockade during fasting prevents the activation of the HPA axis.

Gastrin-releasing peptide (GRP) exerts several functions within the hypothalamus and may be involved in the regulation of pituitary hormone secretion. The purpose of this study was to investigate the central effect of GRP on hypothalamic-pituitary-adrenal axis activity in the male rat. Intracerebroventricular (i.c.v.) but not intravenous administration of GRP (1, 10, 100 ng/rat) increased plasma ACTH and corticosterone concentrations in a dose-dependent manner. The highest dose (100 ng/rat) of GRP increased plasma ACTH and corticosterone 4- and 14-fold, respectively. This increase peaked at 30–60 min after i.c.v. injection, decreased gradually and returned to baseline levels 240 min after GRP administration. The i.c.v. administration of (Leu¹³-ψ-CH₂NH-Leu¹⁴) bombesin, a competitive and specific GRP receptor antagonist, had no effect on ACTH and corticosterone secretion; however, a dose of 1 µg/rat completely blocked the increase of both hormones induced by GRP (10 ng). By using α-helical (9–41) corticotropin-releasing factor (CRF), a competitive antagonist of CRF, the role of CRF on GRP-induced ACTH and corticosterone secretion was also explored. α-Helical (9–41) CRF (10 µg/rat) blocked the increase in ACTH and corticosterone secretion induced by GRP (10 ng). The results obtained in this study suggest that GRP increases the secretion of ACTH and corticosterone in the plasma by acting centrally on GRP receptors, and that endogenous GRP receptor ligands do not tonically regulate ACTH and corticosterone secretion. Furthermore, the hypothalamus-pituitary-adrenal-activating effects induced by GRP appear to be mediated, at least in part, by CRF.

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