/ eh11 5010 Mp 519 Wednesday Jul 16 05:39 AM EL–PB (v. 62, no. 3) 5010 519 Physiology & Behavior, Vol. 62, No. 3, pp. 519–523, 1997 Copyright  1997 Elsevier Science Inc. Printed in the USA. All rights reserved 0031-9384/97 $17.00 / .00 PII S0031-9384( 97 ) 00010-3 Adrenalectomy Lowers the Body Weight Set-Point in Rats CAROLINE GOSSELIN AND MICHEL CABANAC 1 De ´partement de physiologie, Faculte ´ de me ´decine, Universite ´ Laval, Que ´bec Canada G1K 7P4 Received 25 September 1996; Accepted 23 January 1997 GOSSELIN, C. AND M. CABANAC. Adrenalectomy lowers the body weight set-point in rats. PHYSIOL BEHAV 62 (3) 519– 523, 1997.—In order to evaluate the impact of a complete depletion of glucocorticoids on rats’ body weight set-point, rats were adrenalectomized, and their set-points were estimated before, and after surgery. Body weight set-points were obtained from a quantitative behavioral method based on the rats’ food-hoarding response to weight deficit. In addition, body fat contents were measured in vivo using a total body electrical conductivity analyzer ( TOBEC ) . The hoarding of food showed that adrenalectomized rats had significantly lower body weight set-points than the sham-operated controls ( 337 { 11 g vs. 385 { 8 g) and were also significantly lighter. TOBEC measurements showed that the sham-operated control rats had a higher body fat content than the adrenalectomized rats ( 16.7 { 1.1% vs. 10.2 { 1.2% ) . The present study demonstrates that adrenalectomy lowers the body weight set-point in rats, suggesting that the concentrations of glucocorticoid hormones, and in turn, the hypothalamic corticotrophin releasing hormone (CRH) participates in the adjustment of the body weight set-point.  1997 Elsevier Science Inc. Energy balance CRH Glucocorticoids Food hoarding 1 To whom requests for correspondence should be addressed. E-mail: michel.cabanac@phs.ulaval.ca IN 1969, Hervey (17) hypothesized that the regulated variable responsible for body weight stability, was likely to be the blood concentration of a steroid hormone. As steroids are soluble in fat, he argued, their concentration would vary according to the size of the body fat compartment. Recently, this hypothesis was re- vived (9) and blood concentration of glucocorticoids was pro- posed as the regulated variable, rather than the sexual steroids as hypothesized by Hervey. The set-point for the regulation of the glucocorticoid concentration, and in turn body weight, would be adjusted by the hypothalamic corticotrophin releasing hormone (CRH) (8,24,28). One way to affect drastically the blood con- centration of glucocorticoids is by performing bilateral adrenal- ectomy. The aim of the present study is to further investigate the above hypothesis, by measuring body weight set-points of rats before, and after adrenalectomy. If the hypothesis holds true, ad- renalectomized rats should have a lower body weight set-point than normal rats. The effects of bilateral adrenalectomy (ADX) on energy bal- ance are well documented. ADX induces a 20–30% decline in feeding, depletes glycogen reserves, alters carbohydrate and fat metabolisms, and reduces fat deposition ( 30,31,33 ) . ADX is also known to prevent, or cure, obesity in male and female rats, by normalizing their food intake, by increasing their sympathetic nervous system activity and reducing their parasympathetic ac- tivity ( 18,23,27,32,34 ) . For the purpose of the present study, the effects of ADX were measured on the threshold of food hoarding. It should be kept in mind that the rat’s hoarding behavior used to estimate the set-point, is a reflection of the regulated system at work responding to weight deficit. Hoarding behavior offers a simple, quantitative, and reliable technique to evaluate a rat’s body weight set-point. The hoarding response, following a weight disturbance below or beyond the animal’s set-point, is a predictable behavior that can be described by the linear equation: y Å0ax / b ; where y is the amount of food hoarded, x the rat’s body weight, a the negative slope of the regression line, and b , the ordinate at zero abscissa (13). The hoarding threshold, the intercept of this regression line with the X axis defines the rat’s body weight set-point (7,8,10,12). METHODS Animals Ten male Sprague–Dawley rats from Charles River Inc. of Canada ( five ADX, and five controls ) were used as subjects; their weights ranged from 300 to 350 g at the beginning of the exper- iment. Upon arrival, at week zero, the rats were trained to feed once a day from 0830 to 1030 h. We kept the same feeding schedule throughout the experiment, except on week 3 after ad- renalectomy, and on week 6 ( including two weekends ) when the rats were fed ad lib 24 h/day. Light went on at 1800 and off at 0600 h. The rats were weighed every morning, five days a week, before any other measurement was done. All the rats were housed in the same room, in individual wire-meshed, steel-walled rabbit cages (0.48 m 1 0.41 m 1 0.34 m). Hoarding In each cage, the rat had permanent access to a home (0.24 m 1 0.19 m 1 0.10 m) made of a plastic container painted black,