Neurobehavioral protective effects of Japanese sake yeast supplement against chronic stress-induced anxiety and depression-like symptoms in mice: Possible role of central adenosine receptors.

Rationale: Using routine synthetic drugs in the treatment of psychiatric disorders may have some restrictions due to serious side effects and pharmacoresistance. Some natural agents may be promising alternatives in this case. The neuroprotective activity of the neuromodulator adenosine and its receptor, A receptor (AR) in the central nervous system has been mentioned in different studies.

Objective: We aimed to determine the anxiolytic, antidepressant and sedative effects of Japanese sake yeast as the first report.

Method: Mice were subjected to a one-week stress protocol and concomitantly treated orally with sake yeast at the dose levels of 100, 200 and 300 mg kg once daily for a week. The anxiolytic, antidepressant, and sedative actions of sake yeast were evaluated with the related tests.

Results: In all dose regiments, sake yeast significantly improved functions in the EPM and FST. 200 and 300 mg/kg of sake yeast significantly increased sleep duration and reduced sleep latency. Anxiolytic and antidepressant-like activities of sake yeast were maintained by the injection of ZM241385 (15 mg kg), a selective adenosine AR antagonist but completely counteracted by the injection of 8-cyclopentyltheophylline (10 mg kg), a selective adenosine AR antagonist. 300 mg/kg of the yeast significantly increased the BDNF levels. Amygdala corticosterone levels did not show any significant changes at any dosage. Amygdala TNF-α, IL-6 and IL-1β levels also decreased significantly with all the sake regiments compared to the control group.

Conclusions: We conclude that oral sake yeast supplement exerts a neurobehavioral protective effect predominantly by activating central ARs.