Studies on peripheral administration of selective bombesin receptor-2 (BB₂) ligands and BB₂ knockout mice have shown that stimulation of BB₂ receptors reduces food intake in rodents. Few studies, however, have described responses to centrally administered BB₂ ligands (see Merali et al., 1999). Our aim, therefore, was to investigate the effect of administration of a novel, potent and selective BB₂ 'agonist' on food intake in rats.

Male Sprague-Dawley rats (300-310g) were fitted with a cannula into the lateral brain ventricle. Beginning one week later and following an overnight fast, they were administered bombesin (0.3, 1.0 or 3.0nmol), or the potent, selective BB₂ agonist [Glp⁷, ßAla¹¹, Phe¹³, Nle¹⁴]Bn(7-14) amide (Darker et al., 2001) (0.6, 1.0, 3.0nmol), or the two compounds together (both 1nmol). The BB₂ agonist was also given during the morning to freely feeding rats. In each experiment, each rat received each treatment in a Latin square design, there being a week between treatments. Results were analysed by one-way ANOVA with Dunnett's multiple comparison post-test; n=6 (overnight fasted) or 4 (freely fed animals).

In a preliminary study, bombesin reduced food intake in re-fed rats in a dose-responsive manner. Food intake in saline-treated rats was 5.29 ± 0.64 , 6.12 ± 0.62 and 7.16 ± 0.66g (means ± s.e.mean) over 0-1, 0-2 and 0-4h respectively. All three doses reduced food intake significantly (54 ± 14, 76 ± 14 and 78 ± 11 % suppression) over 1 hour (P<0.01); the two higher doses were effective over 2 hours (P<0.01); and the highest dose (3nmol) was effective over 4hours (P<0.05). In a second experiment, bombesin (1nmol) again reduced food intake in re-fed rats (Table 1). The BB₂ agonist alone (1nmol) had no effect in the re-fed rats, but it blocked the anorexic effect of bombesin (1nmol), the 0-2 and 0-4h food intake actually being greater than in vehicle (in this experiment, water) -treated rats.

***P<0.001 compared to no treatment.
The BB₂ agonist alone (1nmol) also had no effect in freely fed rats.

Blockade of the anorexic effect of the BB₁ plus BB₂ agonist bombesin by a compound that is a potent agonist of cloned BB₂ receptors raises the possibility that it is a low efficacy agonist and behaves as an antagonist in vitro, where receptor number or coupling to the response may be lower. Why it should reveal an orexigenic effect of bombesin is unclear, however.

Darker et al., 2001 J.Peptide Sci. 7, 598-605.
Merali et al., 1999 Neuropeptides 33, 376-386.