Long-term moderate caloric restriction and social isolation synergize to induce anorexia-like behavior in rats

Moderate caloric restriction (CR) is an effective strategy to delay the onset of chronic disease states. Conversely, social isolation (SI) carries an increased risk of morbidity and mortality from several causes. The present studies were designed to investigate the long-term effect of the two combined exposures. Two-month-old male rats of the Fischer 344 strain were fed either ad libitum or under a regimen of CR, and each of the two animal sets were housed either in group or isolation. Food consumption and animal growth curves were as expected during the first 6 wk of observation. However, starting at 2 mo and continuing until the fifth month of follow up, rats exposed to both CR and SI showed signs of altered feeding behavior and were unable to complete their (already restricted) meal. Furthermore, altered behavior was accompanied by a corresponding decrease in growth rate until no further increase in body weight was observed. Restoration of group-housing conditions led to a reversal of this phenotype. We conclude that chronic moderate CR and SI synergize to induce anorexia-like behavior, representing a simple and reproducible model to study such an eating disorder.