Intraventricular corticosterone increases the rate of body weight gain in underweight adrenalectomized rats

Circulating glucocorticoids are necessary for hyperphagia and excessive weight gain in obese rodents. It has been reported that intraventricular administration of selected glucocorticoids restores hyperphagia and weight gain in anorexic adrenalectomized gold thioglucose-treated mice. We wanted to determine whether administration of glucocorticoids directly into the central nervous system of normal (nonobese) rats will enhance the rate of weight gain. In the initial experiment rats were allowed ad libitum access to chow or were rendered underweight by a 7- to 10-day period of food restriction. Animals were then adrenalectomized or sham operated and allowed ad libitum access to chow. Both groups of adrenalectomized animals consumed less food and gained weight less rapidly than their respective sham controls. Previously food-restricted and therefore underweight adrenalectomized rats consumed significantly more food and gained weight more rapidly than previously ad libitum-fed adrenalectomized rats. These data support the conclusion that adrenalectomized rats, like intact rats, regulate their weight, albeit at a lower level than intact rats. To determine a possible role of central glucocorticoids in this phenomenon, food-restricted or ad libitum-fed rats received a single intraventricular injection of corticosterone or its vehicle on the day after adrenalectomy or sham surgery. Whereas intraventricular corticosterone had no effect on weight gain in ad libitum-fed rats, it significantly increased the rate of weight gain in food-restricted adrenalectomized rats relative to that in vehicle-treated controls. Peripheral administration of corticosterone had no effect in this paradigm. It is concluded that glucocorticoids act directly on the central nervous system of underweight lean rats to augment weight gain.