The importance of corticosterone in mediating restraint-induced weight loss in rats

Abstract

I. J. Scherer, P. V. Holmes, R. B.S. Harris. The importance of corticosterone in mediating restraint-induced weight loss in rats. PHYSIOL BEHAV 00 (0) 000-000, 2010. Rats restrained for 3 h/day for 3d ays (RR) lose weight and do not return to the weight of non-restrained controls once restraint has ended. This study tested the importance of restraint-induced corticosterone release in mediating the change in body weight by injecting ADX rats with 2.0mg corticosterone/kg before each restraint to replicate the restraint-induced surge in circulating corticosterone. Restrained adrenalectomized (ADX) rats injected with corticosterone had the same initial weight loss as intact restrained rats, whereas corticosterone injection in non-restrained ADX rats and restraint of ADX rats injected with saline each produced only half as much initial weight loss. Sustained weight loss, measured for 14 days after the end of RR, was the same for restrained intact rats and restrained ADX rats injected with corticosterone whereas restrained ADX rats injected with saline achieved the same weight gain as their controls. Corticosterone injections had no effect on weight gain of non-restrained intact rats. In situ hybridization showed that corticotropin releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus (PVN) was increased by the same degree in ADX rats and restrained intact rats and was not modified by corticosterone injections. There was no significant effect of restraint, ADX or corticosterone injection on PVN arginine vasopressin (AVP) mRNA expression. These data indicate that a surge in corticosterone causes sustained weight loss in ADX rats through a mechanism that can be compensated for in intact rats and is independent of changes in PVN CRF or AVP mRNA expression.

Figure 1

Serum corticosterone of rats (n=3) injected with 1.0 mg/kg corticosterone or subjected to 3 hours of restraint in the pilot study. This dose of corticosterone was doubled in order to replicate the release of corticosterone in rats restrained for 3 hours (see Figure 4 for results from Experiment 1).

Figure 2

Body weight change of rats in Experiment 1. Data are means ± sem for groups of 9 or 10 rats. Asterisks in Panels A to C indicate significant differences between CTRL and RR rats within each treatment group. Panel D shows the average weight change of each group of rats during the three days of restraint and Panel E shows the average change in weight for each group from the morning immediately before the first restraint to 13 days after the end of restraint, the last day of the experiment. Data in panels D or E that do not share a common superscript are significantly different at P<0.05.

Figure 3

Food intake of rats in Experiment 1. Data are means ± sem for groups of 9 or 10 rats. Asterisks in Panels A to C indicate significant differences between CTRL and RR rats within each treatment group. Total three day food intake (Panel D) of each group of rats before, during and after restraint. Values for 3 day intake on the days of restraint that do not share a common superscript are significantly different at P<0.05.

Figure 4

Serum corticosterone levels measured on Day 2 of RR in Experiment 1 are shown in Panel A and average area under the curve for each group is shown in Panel B. Data are means ± sem for groups of 9 or 10 rats and values that do not share a common superscript are significantly different.

Figure 5

Body weight change of rats in Experiment 2 (Panel A). Asterisks indicate significant differences between RR rats and the two other groups of rats. Data are means ± sem for groups of 10 rats. Panel B shows the total three day food intake of the different groups of rats before, during and after restraint. Values for intake on the days of restraint that do not share a common superscript are significantly different at P<0.05. Panel C shows serum corticosterone levels measured on Day 2 of RR in Experiment 2, asterisks indicate a significant difference between the CTRL and the RR and CORT groups.

Figure 6

Panel A shows CRF mRNA expression and Panel B shows AVP mRNA expression in the PVN in Experiment 3. Superscript letters indicate significant differences in density of expression between groups (P<0.05).