Mechanisms underlying anorexia after microinjection of bombesin into the lateral cerebroventricle

Intracerebroventricular (i.c.v.) injections of bombesin (BN) and gastrin-releasing peptide (GRP) dose-dependently decreased food intake in male Wistar rats fasted for 17 h. Neuromedin B (NMB) did not show any effect on food intake. After BN administration, locomotor activity did not significantly change, compared with a vehicle-injected group. The anorexia induced by BN (0.3 μg) was perfectly inhibited by pretreatment with a GRP-receptor antagonist, [d-Tyr6]BN(6-13) methyl ester (10 μg), an NO synthase inhibitor, l-nitro-arginine (30 μg), and a PKG inhibitor, H-9 (2 μg). The cGMP concentration in the hypothalamus increased 1 h after administration when compared with the vehicle-injected group. On the other hand, an NMB-receptor antagonist, BIM23127 (10 μg), and the protein kinase (PK) C inhibitors, chelerythrine (2 μg) and Gö6983 (2 μg), inhibited only the late phase of the anorexia. A PKC activator, phorbol 12, 13-dibutyrate (3 μg), injected into the ventricle decreased food intake. These findings suggest that BN suppresses food intake mainly mediated through the GRP receptor and NO-cGMP-PKG pathway, and NMB receptor and PKC is partly involved in the late phase of the anorexia.