89 Different Response to Chronic Isolation Stress Between Young and Aged Mice

Abstract

G A A b st ra ct s in ERα in aged mice, ERα agonist was administered and the effect on food intake was investigated. Finally, the effect of 5-HT2CR antagonist on ERα-agonist-induced decrease in food intake in aged mice was examined. Results: Novelty stress significantly and continuously suppressed food intake in aged male mice compared with young or female mice. The decreased food intake in aged male mice exposed to novelty stress was significantly ameliorated by the administration of the aromatase inhibitor letrozole or the 5-HT2CR antagonists SB242084 or rikkunshito, a Kampo medicine (Figure 1, 2). Compared with young male mice, hypothalamic ERα and aromatase mRNA expression levels were significantly increased in aged male mice, whereas ER β mRNA expression levels remained unaltered. There were no differences in plasma estradiol levels between groups. Administration of the ER αagonist significantly and dose-dependently suppressed food intake in aged male mice. Administration of the 5-HT2CR antagonist SB242084 caused marked recovery of the ER α-agonist-induced decrease in food intake in aged male mice. Conclusion: ERα activation occurred in aged male mice and caused 5-HT2CR activation. This may result in a persistent decrease in food intake under novelty stress.