How Creatine Exerts its Antidepressant Effect?

Creatine has been proposed to exert therapeutic effects in the management of depression-like behavior in mice, but the cell signaling pathways involved in its antidepressant effects are not well-known. In order to determine the specific mechanisms involved in the antidepressant effects of creatine, Cunha et al. investigated the involvement of PI3K/Akt pathway, an intracellular signaling pathway directly related to cell cycle[8]. The researchers treated mice with creatine at a dose of 1 mg/kg orally and they were subjected to undergo a tail suspension test to determine antidepressant activity. They observed that the acute treatment of mice with creatine was able to increase the activities of the PI3K/Akt pathway. The researchers therefore concluded that the antidepressant-like effect of creatine in the tail suspension test depends on the activation of the PI3K/Akt pathway.

Interestingly, evidence suggests that brain intracellular signaling systems including the AKT/GSK3 pathway have been found to be altered in patients with major depression and psychiatric illnesses[9]. Because creatine supplementation has been found to improve the activities of the PI3K/Akt pathway in mouse models of depression, there’s a strong possibility that creatine supplementation may also exert therapeutic benefits in people suffering from depressive symptoms.

Conclusion

Vital for optimum brain structure and performance, creatine is critical for a healthy mood and reducing mental distress in mice. Because of its positive effects on certain brain signaling pathways in mouse models, oral creatine supplementation may also help improve depressive symptoms in humans.