The octadecaneuropeptide [diazepam-binding inhibitor (33-50)] exerts potent anorexigenic effects in rodents

The effects of intracerebroventricular administration of the octadecaneuropeptide ODN on food intake have been investigated in rat and mouse. In rats deprived of food from 9:00 a.m. to 7:00 p.m., i.c.v. injection of ODN (30 to 100 ng) provoked a dose-dependent reduction of food consumption during the following 12-h nocturnal period. At a dose of 100 ng, ODN almost completely suppressed food intake. Treatment of rats with diazepam (2 mg/kg s.c.; 15 min before ODN administration) did not affect the anorexigenic response evoked by 100 ng ODN. Continuous i.c.v. infusion of ODN (10 ng/h during 15 days) using osmotic minipumps, significantly reduced food intake during the 2nd, 3rd and 4th days of treatment. The decrease in food consumption was associated with a significant reduction in body weight, which persisted during the 15-day duration of the experiment. In mice deprived of food for 18 h, i.c.v. administration of a low dose of ODN (5 ng) significantly reduced food intake. Treatment of mice with diazepam (1 mg/kg s.c.; 10 min before ODN administration) did not prevent the inhibitory effect of ODN (100 ng) on food intake. The C-terminal octapeptide fragment of ODN mimicked the anorexigenic effect of the intact peptide. Taken together, the present data demonstrate that i.c.v. injection of ODN causes, in both rat and mouse, a long-lasting anorexigenic effect that is not mediated through central-type benzodiazepine receptors. The biologically active region of ODN appears to be located in the C-terminal domain of the peptide.