Pharmaco-ontogeny of bombesin's suppression of food intake and its attenuation by histamine H₃ receptor agonists

Bombesin (BN) administration has been shown to suppress food intake across diverse species. Preliminary results have shown that BN elicits a satiety-like state from postnatal day (PD) 1, through unknown mechanism(s). We have recently shown that in adults rats, α-methyl histamine (α-MH), a selective H₃ receptor agonist that inhibits the release and synthesis of histamine, blocks the feeding suppressant effects of BN. The objective of this study was to determine if such a mechanism was operation at birth or whether it developed over time. Thus effects of histamine H₃ receptor agonists as well as BN-histamine interactions in the regulation of food intake were assessed during early development. On PD. 1, 5, 10 and 15, groups of food deprived Sprague-Dawley rat pups (n = 8-12) were injected with BN alone (0 (saline), 0.006, 0.06 or 0.6 mg/kg, s.c,), H₃ receptor agonists alone (α-MH or Imetit (3 or 5 mg/kg s.c.)) or the combination of BN and H₃ receptor agonists, and their ingestive behavior was monitored. Results confirmed that pups were sensitive to feeding suppressant effects of BN starting from PD 1. Imetit of α-MH either failed to affect food intake or at certain time points enhanced food intake. Pretreatment with the H₃ receptor agonists significantly attenuated the feeding suppressant effects of BN, suggesting that early in ontogeny, BN may suppress food ingestion possibly by facilitating histamine release at some relevant site(s).