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

The effects of intracerebroventricular administration of the octadecaneurop eptide 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 t o 100 ng) provoked a dose-dependent reduction of food consumption during th e following 12-h nocturnal period. At a dose of 100 ng. ODN almost complete ly suppressed food intake. Treatment of rats with diazepam (2 mg/kg s.c.: 1 5 min before ODN administration) did not affect the anorexigenic response e voked by 100 ng ODN. Continuous i.c.v. infusion of ODN (10 ng/h during 15 d ays) using osmotic minipumps. significantly reduced food intake during the 2nd, 3rd and 4th days of treatment. The decrease in food consumption was as sociated with a significant reduction in body weight, which persisted durin g 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 fo od 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 f ood intake. The C-terminal octapeptide fragment of ODN mimicked the anorexi genic effect of the intact peptide. Taken together, the present data demons trate that i.c.v. injection of ODN causes, in both rat and mouse, a long-la sting anorexigenic effect that is not mediated through central-type benzodi azepine receptors. The biologically active region of ODN appears to be loca ted in the C-terminal domain of the peptide. (C) 2001 Elsevier Science B.V. All rights reserved.