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. 2016 Sep;20(3):24-31.
doi: 10.20463/jenb.2016.09.20.3.4. Epub 2016 Sep 30.

Effects of creatine monohydrate supplementation and exercise on depression-like behaviors and raphe 5-HT neurons in mice

Na-Ri Ahn  1 , Yea-Hyun Leem  2 , Morimasa Kato  3 , Hyuk-ki Chang  1
Affiliations

Effects of creatine monohydrate supplementation and exercise on depression-like behaviors and raphe 5-HT neurons in mice

Na-Ri Ahn et al. J Exerc Nutrition Biochem. 2016 Sep.

Abstract

Purpose: 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.

Methods: 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)).

Results: 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.

Conclusion: 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.

Keywords: 5-HT; Antidepressant; Behavior; Creatine; Depression; Exercise.

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Figures

Figure 1.
Figure 1.. The experimental design. This study was conducted over a period of treatment of 5 weeks. From week 2 of CMS treatment, exercise and creatine treatments were performed over 4 weeks.
Figure 2.
Figure 2.. The data of tail suspension test during 4 min. (A) Immobility count (B) Immobility time. Letters a, b, and c indicate significant differences.
Figure 3.
Figure 3.. The data of forced swimming test over 4 min. (A) Immobility count (B) Immobility time. Letters a, b, and c indicate significant differences.
Figure 4.
Figure 4.. 5-HT expression in the dorsal raphe nucleus. (A) Control group (B) Stress group (C) combined stress and creatine intake group (D) combined stress and exercise group (E) combined stress, creatine intake and exercise group (F) the brain map. Aq, cerebral aqueduct; DR, dorsal raphe nucleus; LC, locus coeruleus; MnR, median raphe nucleus (G) bar graphs summarizing the 5-HT expression.
Figure 5.
Figure 5.. 5-HT expression in the median raphe nucleus. (A) Control group (B) Stress group (C) combined stress and creatine intake group (D) combined stress and exercise group (E) combined stress, creatine intake and exercise group (F) the brain map. Aq, cerebral aqueduct; DR, dorsal raphe nucleus; LC, locus coeruleus; MnR, median raphe nucleus (G) bar graphs summarizing the 5-HT expression.
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