A SINGLE INTRACEREBROVENTRICULAR INJECTION OF DEXAMETHASONE ELEVATES FOOD-INTAKE AND PLASMA-INSULIN AND DEPRESSES METABOLIC RATES IN ADRENALECTOMIZED OBESE (OB OB) MICE/

A single intracerebroventricular (ICV) injection of dexamethasone rapi dly (within 30 min to 3 h) increases plasma insulin and suppresses oxy gen consumption in adrenalectomized ob/ob mice with minimal effects in lean mice. Food intake of these adrenalectomized ob/ob mice was unaff ected by ICV dexamethasone during these short-term studies. However, i n a longer-term study with adrenalectomized gold thioglucose-lesioned obese mice, food intake increased fourfold 6-8 d after a single ICV in jection of dexamethasone. We have now further examined the time course of dexamethasone actions in adrenalectomized ob/ob and lean mice in t he 96-h post-injection period. A single ICV injection of dexamethasone increased food intake 32% and plasma insulin 81%, and depressed oxyge n consumption 11%, in adrenalectomized ob/ob mice during the 24-h peri od after injection, without increasing food intake or plasma insulin i n lean mice. Oxygen consumption was 14% lower in lean mice 24 and 48 h after dexamethasone injection relative to saline-injected lean mice. Food intake and oxygen consumption in ob/ob mice returned to levels in saline-injected controls at 48 and 72 h after injection, respectively . Oxygen consumption of lean mice also returned to control levels at 7 2 h post-injection. Plasma insulin concentrations were similar in dexa methasone- and saline-treated ob/ob and lean mice at 96 h post-injecti on (the only time point examined other than 24 h). A single ICV inject ion of dexamethasone exerts both rapid (within 30 min to 3 h) and sust ained (days) metabolic actions in ob/ob mice.