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 adult rats, alpha-methyl histamine (alpha-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 (alpha-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 or alpha-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).