EFFECTS OF REPEATED INTRAVENOUS ADMINISTRATION OF DIAZEPAM ON FOOD-INTAKE IN RATS

Effects of repeated intravenous (iv) administration of diazepam on food intake were investigated in freely moving rats implanted with a chronic iv cannula. Diazepam (0.2 and 2 mg/kg) was automatically injected iv at 3-h intervals for 3 consecutive days. Food intake was measured twice daily, ie for the light phase (700-1900) and dark phase (1900-700). Food intake during the light phase was increased in a dose-dependent manner following diazepam. Each injection of diazepam provoked hyperphagia, followed by a compensatory hypophagia until the next diazepam injection. Body weight, however, was increased significantly in rats treated with diazepam. When diazepam (2 mg/kg) was automatically injected at 3-h intervals for 10 consecutive days, tolerance did not develop to the hyperphagia and body weight was increased significantly following diazepam injection. After cessation of diazepam injection, both food intake and body weight decreased. These findings suggest that such excessive iv treatment with diazepam induces hyperphagia showing no tolerance accompanied by an increase in body weight, thus resulting in a trend toward obesity in rats.