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

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de Mateos-Verchere, Juanita | Leprince, Jérôme | Tonon, Marie-Christine | Vaudry, Hubert | Costentin, Jean

Edité par CCSD ; Elsevier -

International audience. 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.

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