Chronic food restriction in young rats results in depression- and anxiety-like behaviors with decreased expression of serotonin reuptake transporter

Abstract Evidence of semi-starvation is commonly found in patients with eating disorders. This study was conducted to examine the adverse effects of chronic caloric restriction in young rats, since there have been increasing incidence of eating disorders especially among young populations. Food restriction group was supplied daily with 50% of chow consumed by its ad libitum fed control group from postnatal day 28. After 5 weeks of food restriction, brain contents of serotonin (5-hydroxy-tryptamine; 5-HT) and its metabolite 5-hydroxyindol acetic acid were analyzed by high-performance liquid chromatography and mRNA expression of 5-HT reuptake transporter (5-HTT) by in situ hybridization. Plasma corticosterone levels were determined by radioimmunoassay. Behavioral assessments were performed with Porsolt swim test for depressive behavior and with elevated plus maze test for anxiety. Five weeks of food restriction markedly increased plasma level of corticosterone, and significantly decreased 5-HT turnover rates in the hippocampus and the hypothalamus. 5-HTT mRNA expression decreased in the raphe nucleus of food restricted rats compared with free fed controls. Immobility time during the swim test increased in the food restricted group, compared to the control group. Food restricted rats spent more time in the closed arms, less time in the open arms, of elevated plus maze compared with control rats. These results suggest that chronic caloric restriction in young rats may lead to the development of depressive and/or anxiety disorders, likely, in relation with dysfunction of brain 5-HT system.