Desmethionine-bombesin receptor antagonist blocks bombesin-induced inhibition of alcohol intake.

ABSTRACT

[D-Phe6,Des-Met14]bombesin(6-14), ethyl amide (D-BN) is a specific, competitive receptor antagonist of bombesin, a neuropeptide that inhibits alcohol and food intake. We tested the effects of IP injected D-BN (4-400 micrograms/kg) on bombesin-induced (4 micrograms/kg) reduction of caloric intake. In the first experiment, ad lib-fed female and male rats (Ns = 18) were deprived of water for 23 h, injected with peptides or saline in randomized sequences of doses, and immediately given access to 5% w/v ethanol for 30 min, followed by 30 min of water. In a second experiment, male rats (N = 10) were injected with the antagonist at 10 or 20 min prior to bombesin injection and alcohol access, and behaviors were observed and quantified once a minute with an instantaneous time-sampling technique. D-BN injection blocked the bombesin-induced reduction in alcohol intake (> or = 40 micrograms/kg) and food intake (> or = 200 micrograms/kg). When injected 20 min prior to access, D-BN alone (200 micrograms/kg) initially elevated alcohol drinking and later increased feeding behaviors and decreased resting, relative to saline injection. Results indicate bombesin-induced reduction of alcohol intake depends on a specific peptidergic receptor process, and endogenous bombesin-like peptide could act physiologically to elicit satiation with ethanol and food.