Fourth ventricular injection of the bombesin receptor antagonist [D-Phe6]bombesin(6-13)methyl ester, but not BW2258U89, increases food intake in rats.

To investigate the role of endogenous bombesin-like peptides in the caudal brainstem for the short-term control of food intake, we evaluated the effects of fourth-ventricular injections of two different bombesin (BN) receptor antagonists, [D-Phe6]BN(6-13) methyl ester and BW2258U89, on intake of sweetened, condensed milk in male rats. Although fourth-ventricular administration of BW2258U89 (0.125-20 ng) had no effect on food intake, fourth-ventricular injections of 1.0-20.0 ng of [D-Phe6BN(6-13) methyl ester resulted in an inverted U-shaped, dose-response curve with a maximal effect at 2.5 ng. Microstructural analysis of the licking behavior indicated that the increase in intake was primarily the result of an increased number of licks and an increase in lick efficiency. Behavioral time sampling demonstrated that these changes in intake occurred without the appearance of any competing behavior or significant change in the overall pattern of behavior. Because [D-Phe6BN(6-13) methyl ester appears to be a preferential antagonist at the GRP-preferring receptor, the increased intake that occurred after its administration suggests that an endogenous GRP-mechanism in the caudal brainstem is necessary for the normal, short-term control of sweet milk intake under these conditions.