The Impact of Chronic Social Stress on Emotional Behavior in Mice and the Therapeutic Effect of Peripheral Mild-Heat Stimulation

In today’s stressful society, mental diseases such as adjustment disorder, affective disorders including anxiety and depression, and chronic fatigue syndrome could be attributed to social stress and are considered as serious social problems. It has been long known in the acupuncture and moxibustion therapies in Japan and China that stimulation at Zhongwan and Taichong points have effects on stress-related anxiety and depression. In the present study, we therefore tested the effect of peripheral mild-heat stimulation at Zhongwan and Taichong on anxiety and brain biochemistry using a mouse model of chronic social stress. Male ddY mice (4 weeks old) were stressed by isolated rearing for 6 weeks. They received mild-heat stimulation (43 ̊C for 5 min) at Zhongwan and Taichong under isoflurane anesthesia after 4 weeks of the social isolation 3 times a week for 2 weeks, using the “Stress Free Apparatus” (Ryoken Co., Ltd). Control mice received only isoflurane anesthesia. Group-reared mice also underwent the same stimulus/anesthesia sessions. Two days after the last peripheral heat stimulation, anxiety was determined by the light/dark box test as the time spent in the light compartment and the number of transfer between the light and dark compartments. Before and after the last stimulation, blood was collected from an artery at the back of