Study On Mechanisms Of Transcutaneous Electical Nerve Stimulation Of Auricular Concha Underlying Improvement Of Depressive Behavior In Depression Rats

Objective:To observe the effect of transcutaneous electrical nerve stimulation(TENS) of auricular concha region(ACR) at different time points on the depressive status of model rats, and to explore its mechanisms underlying improvement of depression.Methods:A total of100male Wistar rats were randomized into normal(n=10), CUMS mode(n=10), TENS-ACR(n=10), preventive TENS-ACR(Pre-TENS-ACR, n=10) and TENS-ear-tip (n=10) groups. Every5rats in normal group were housed in one box with normal breeding. Rats in the depression model, TENS-ACR, Pre-TENS-ACR, TENS-ear-tip groups were placed in separate boxes after7days acclimatized period. Depression model was induced by chronic unpredictable mild stress(CUMS), including food deprivation, water deprivation, cage tilt45℃, forced swimming in ice water4℃, clipping tail3min,50V electric shock and overnight illumination, and isolated breeding for21days. Before CUMS, every rat was accepted on open field test, rats with30-120of total score were selected. TENS was not applied to rats in the normal group and model group, while rats in model group accepted inhaled anesthesia in the same way. TENS (2Hz,1mA) was applied to the bilateral ACR for20min for rats in the TENS-ACR group, once daily for14days. TENS was applied to the bilateral Ear-tips of rats in TENS-ear-tip group for20min, once daily for14days. Rats in the TENS-ACR group and TENS-ear-tip group were continuously bred after TENS for14days to assess behavioral changes. Open-field test and sucrose solution intake preference test were conducted to assess changes of the rats’behavior activities before modeling and on day22,36and50after modeling. Heart rate and blood pressure(systolic pressure and diastolic pressure) of rats in the model, TENS-ACR and TENS-ear-tip groups were monitored noninvasively under inhaled anesthesia and recorded at the timepoints of anesthesia0min (pre-TENS),1min (TENS0 min),6min (TENS5min),11min (TENS10min),16min (TENS15min),21min (TENS20min). At the end of this study, venous blood was sampled for measurement of plasma cotisol and ACTH by ELISA, R&D, USA). We also took20male Wistar rats for TENS-ACR group(W) in winter, and10rats for assessing behavioral and biochemical changes so as to compare the different manifestation in different season.Results:1. Descending speed and range of blood pressure and heart rate of TENS-ACR group were significantly different with those at the model group and TENS-ear-tip group.2. In comparison with pre-modeling, the percentages of sucrose solution consumption in rats of the model group were decreased gradually from day22to50(P>0.05). Compared with the model group, the percentage of sucrose solution consumption in the TENS-ACR group was increased significantly on day50(P<0.05), suggesting an inhibitory effect of TENS on the reduction of sucrose intake preference at this time-point. No significant differences were found between pre-TENS-ACR and the model groups and between the TENS-ear-tip and model groups as well as between the TENS-ACR and model groups at most time-points(P>0.05). Open-field test showed that in comparison with pre-modeling in the same one group, the total scores, crossing and rearing scores on day22were decreased considerably in the model and TENS-ear-tip groups(P<0.05, P<0.01), rather than in the pre-TENS-ACR and TENS-ACR groups(P>0.05), suggesting a suppressing effect of pre-TENS-ACR and TENS-ACR on depression behavior. Compared to day22in the same one group, the total scores, crossing and rearing scores on day36and50in the pre TENS-ACR and TENS-ear-tip groups were decreased significantly(P<0.05, P<0.01).3. No marked effects of TENS-ACR on sugar water consumption and motor behavior were found(P>0.05), but slight reduction was observed in TENS-ACR(W).4. Plasma cortisol and ACTH levels of the model(cortisol50.28ng/ml, ACTH162.2pg/ml) were significantly higher than those of the normal(cortisol 24.61ng/ml, ACTH82.71pg/ml). In comparison with the model group, no significant differences were found between TENS-ACR(cortisol39.64ng/ml, ACTH111.95pg/ml) and TENS-ear-tip groups(cortisol39.43ng/ml, ACTH86.87pg/ml). Open-field test scores of the TENS-ACR group (45.33of group mean score at the ending time point) was obviously higher(P<0.05) than those of the TENS-ear-tip group (26.92) and model group (9.33).5. No significant difference were found between the summer and winter seasons in the regulative effect of AE-ACR on plasma cortisol and ACTH(P>0.05).Conclusion:1. It is a wholly systematic process through multipath mechanism that the adjustment of TENS-ACR on depressive status of CUMS model rats, and the mechanism of auricular vagus nerve appeared more clearly.2. In the condition of isolate accommodation, TENS-ACR can restrain the development of depressively behavioral status of the model rats, the effect of TENS-ACR group is better than preventive-TENS-ACR in Open-field test.3. Fourteen days’ AVNES intervention effectively relieves the depressive status in summer but not in winter.4. TENS-ear-tip can suppress plasma ACTH level but has no effect on plasma cortisol.5. TENS-ACR suppresses plasma cortisol quickly but shortly, and reduces plasma ACTH long but mildly.