Toxic effect of aberrant light/dark cycle on depression and other symptoms induced by chronic corticosterone treatment in mice

Abstract

Circadian rhythm governs almost all mammalian organs. Impairment of circadian rhythm causes dysfunction of physiological systems, which sometimes affects the pathogenesis and development of various diseases. Depression is one of the most common diseases that relate to circadian rhythms. In this study, we analyzed the effects of daily light/dark (LD) conditions on the symptoms induced by corticosterone. Chronic corticosterone treatment induces depression-like symptom, and is widely used to develop and analyze depression in rodents. Male adult C57BL/6N mice were maintained in a normal light/dark (LD) cycle of 12 hours light and 12 hours dark (LD12:12), short day conditions of 6 hours light and 18 hours dark (LD6:18), or long day conditions of 21 hours light and 3 hours dark (LD21:3). Mice were exposed to 35 mg/L of corticosterone or vehicle in the drinking water. Mice were divided into 4 groups: control, corticosterone, aberrant LD (LD6:18 or LD21:3), and corticosterone + aberrant LD. After 6 weeks of exposure, open field test, LD box test, tail suspension test, and novelty suppressed feeding test were conducted to detect depression-and anxiety-like symptoms. Corticosterone treatment induced body weight gain and depression/anxiety-like symptoms. Although the short or long photoperiod alone induced little changes, the aberrant LD exacerbated the corticosterone-induced symptoms. Mice with corticosterone+LD6:18 showed larger changes in novelty suppressed feeding test than mice with corticosterone. Short photoperiod seemed to worsen corticosterone-induced depression. On the other hand, the long photoperiod showed no obvious effects on mood. However, mice with corticosterone+LD21:3 showed larger weight gain than mice with corticosterone. Long photoperiod seemed to enhance corticosterone-induced weight gain. These results indicated that aberrant LD could act as an exacerbating factor for corticosterone-induced symptoms, and that long and short photoperiod have different physiological effects on mood and weight control. Since people are usually exposed to various stresses and risk factors, aberrant LD cycle might have a large impact on their health. Mice with corticosterone + aberrant LD might be a useful animal model for investigating the effects of LD conditions on depression, obesity, and other symptoms in such stressful circumstances.