Sa1396 Potential New Treatment to Alleviate Stress-Induced Anorexia

Abstract

Background/Aim: Exposure to a novel environment causes anxiety and depressed reactions and is well-known to provoke various gastrointestinal symptoms like anorexia. However, the mechanism underlying this behavior is unclear and there has not been approached to that the anorexia. The present study aimed to clarify the role of corticotrophin-releasing factor (CRF) and serotonin (5-HT) receptors in mice exposed to novel environment stress and attempted to discover a new treatment method for improving gastrointestinal tract dysfunction caused by stress. Methods: Male C57BL/6J mice (6-week-old) were housed in groups (n = 5/cage) for one week and acclimated to their environment, following which they were fasted for 24 h. Next, they were moved to isolated cages to induce novel environment stress. We analyzed the expression of stressand appetite-related genes in the hypothalamus and gastric corpus after the exposure to the stress. In addition, we administered a CRF receptor antagonist and various 5-HT receptor antagonists to study their effects on the decreased food intake. Results: Mice exposed to novel environment stress demonstrated a significant increase in the expression of CRF, CRF1 receptor, urocortin, and urocortin 2 genes in the hypothalamus compared with the mice housed in groups. The expression of urocortin 3 and CRF2 receptor genes was unaffected. Moreover, the mice exposed to stress showed an increase or tended to have an increase in the hypothalamic expression of 5HT1a, 5-HT1b, and 5-HT2c receptor genes, and gastric expression of 5-HT2b receptor genes. Administration of the receptor antagonists for CRF1 (NBI27914), 5-HT1b (SB224289), 5-HT2b (SB215505 and SB204741), and 5-HT2c (SB242084) significantly inhibited the decreased food intake caused by novel environment stress. Furthermore, rikkunshito, which has an antagonist action on CRF1, 5-HT2c, and 5-HT2b receptors, clearly inhibited the decrease in food intake after exposure to the stress. Conclusion: The decrease in feeding behavior exposed to novel environment stress is primarily controlled by the signaling of the CRF1, 5-HT1b, 5-HT2b, and 5-HT2c receptors. Drugs that block the signal transmission of these receptors are expected to be appropriate for the potential treatment for anorexia caused by stress.