title: Effects of creatine monohydrate supplementation and exercise on depression-like behaviors and raphe 5-HT neurons in mice.
abstract: The effects of creatine and exercise on chronic stress-induced depression are unclear. In the present study, we identified the effects of 4-week supplementation of creatine monohydrate and/or exercise on antidepressant behavior and raphe 5-HT expression in a chronic mild stress-induced depressed mouse model.
  
  
  
  Seven-week-old male C57BL/6 mice (n=48) were divided randomly into 5 groups: (1) non-stress control (CON, n=10), (2) stress control (ST-CON, n=10), (3) stress and creatine intake (ST-Cr, n=10), (4) stress and exercise (ST-Ex, n=9), and (5) combined stress, exercise, and creatine intake (ST-Cr+Ex, n=9). After five weeks' treatment, we investigated using both anti-behavior tests (the Tail Suspension Test (TST) and the Forced Swimming Test (FST)), and 5-HT expression in the raphe nuclei (the dorsal raphe (DR) and median raphe (MnR)).
  
  
  
  Stress for 4 weeks significantly increased depressive behaviors in the mice. Treatment with creatine supplementation combined with exercise significantly decreased depressive behaviors as compared with the CON-ST group in both the TST and FST tests. With stress, 5-HT expression in the raphe nuclei decreased significantly. With combined creatine and exercise, 5-HT positive cells increased significantly and had a synergic effect on both DR and MnR.
  
  
  
  The present study found that even a single treatment of creatine or exercise has partial effects as an antidepressant in mice with chronic mild stress-induced depression. Furthermore, combined creatine and exercise has synergic effects and is a more effective prescription than a single treatment.
authors.affiliation: Laboratory of Exercise Physiology, Department of Human Movement Science, Seoul Women's University, Seoul Republic of Korea.
authors.forename: Na-Ri
authors.initials: NR
authors.lastname: Ahn
authors.affiliation: Department of Neuroscience and TIDRC, Ewha Womans University Medical Center, Seoul Republic of Korea.
authors.forename: Yea-Hyun
authors.initials: YH
authors.lastname: Leem
authors.affiliation: Department of Health and Nutrition, Yonezawa Nutrition University of Yamagata Prefecture, Yonezawa Japan.
authors.forename: Morimasa
authors.initials: M
authors.lastname: Kato
authors.affiliation: Laboratory of Exercise Physiology, Department of Human Movement Science, Seoul Women's University, Seoul Republic of Korea.
authors.forename: Hyuk-ki
authors.initials: HK
authors.lastname: Chang
keywords: 5-HT; Antidepressant; Behavior; Creatine; Depression; Exercise