The antidepressant effect of albiflorin based on TSPO and mechanism / 中国药理学通报

Aim To study the antidepressant effects of albiflorin and its relationship with TSPO(translocator protein 18 ku). Methods Mice were divided into eight groups(control group, chronic unpredictable stress group, fluoxetine group, albiflorin low, medium, high dose groups, PK11195 group, PK11195+ albiflorin high dose group)based on the data of the behavioral tests conducted to assess the antidepressant-like effects of albiflorin. After the behavioral tests Western blot and ELISA were conducted to evaluate the TSPO expression, progesterone and allopregnanolone level in hippocampus of mice. Results In the behavioral tests, there were significant differences between the model group and the control group, which indicated that the model was successfully established. The positive drug and albiflorin in different dose groups could reverse the effects of the model group, and PK11195 could reverse the effects of paeoniflorin in high dose group. The results of Western blot and ELISA showed that the TSPO expression, progesterone and allopregnanolone level in the model group significantly decreased. The positive drug and albiflorin groups with different doses could reverse the effects of the model group, and PK11195 could reverse the effects of the high dose group. Conclusions Albiflorin has significant antidepressant and antianxiety effects on CUS mice by TSPO, which provides experimental basis for the further study on the antidepressant effects and mechanism of albiflorin in the future.

Effect of Xiaoyaosan on Changes of JAK/STAT Pathway in Hypothalamic Arcuate Nuclei of Rats With Chronic Mild Unpredictable Stress / 中国实验方剂学杂志

Objective:To observe the changes of leptin receptor-tyrosine kinase Janus2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） pathway and the regulatory effect of Xiaoyaosan on the hypothalamic arcuate nuclei of rats with chronic mild unpredictable stress model （CUMS）. Method:Sixty male sprague-dawley rats were randomly divided into normal group， model group， Xiaoyaosan group， and fluoxetine group. After one-week adaptive feeding， the rats in model group， Xiaoyaosan group and fluoxetine group were uesd to replicate the chronic psychological stress rat model through mild unpredictable stimulation. Meanwhile ， they were simultaneously administered the corresponding drugs， Xiaoyaosan 19.27 g·kg-1·d-1， Fluoxetine 2 mg·kg-1·d-1 （based on the average adult body weight of 60 kg）， the rats in the normal group and the model group were given the same volume of normal saline for 6 weeks. The body weight， food intake， sucrose consumption ratios， and the experimental behavior in the open field test （OFT） of the groups were observed. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expressions of ob-R， JAK2， and STAT3 in the arcuate nucleus of rat hypothalamus. Result:Compared with the normal group， the body weight and food intake of the model group were significantly decreased （P<0.05， P<0.01）， the sucrose consumption ratios ， the total behavioral distance of the experimental field and the total distance of the central area were significantly reduced， the protein and mRNA expressions of ob-R， JAK2， STAT3 in the arcuate nucleus of hypothalamus in rats increased significantly （P<0.05， P<0.01）. Compared with the model group， the body weight of Xiaoyaosan group increased significantly on the 7th， 14th， 21st and 28th days （P<0.05， P<0.01）， the food intake of rats increased significantly on the 21st and 35th days of the experiment （P<0.05）， and the sucrose consumption ratios， the total distance of the experimental behavior in the open field test （OFT） and the total distance of the central area were significantly improved. Xiaoyaosan had a corresponding regulatory effect on the protein and mRNA expressions of ob-R， JAK2， STAT3 in the arcuate nucleus of hypothalamus in model rats （P<0.05， P<0.01）. Conclusion:Xiaoyaosan regulates the body weight， appetite， and energy metabolism of chronically mild and unpredictable stress rats， which may be related to the ob-R-JAK2/STAT3 pathway in the hypothalamic arcuate nucleus.

Study on construction of rat model of acute pancreatitis with syndrome of liver depression and Qi stagnation / 中国中药杂志

The aim of this paper was to construct a rat model of acute pancreatitis(AP) with syndrome of liver depression and Qi stagnation, and provide evaluation tools for pharmacodynamic research and efficacy network verification of related traditional Chinese medicine in view of the etiology, pathogenesis and clinical manifestations of AP. According to the Chinese and Western medicine diagnosis and treatment guidelines for AP with syndrome of liver depression and Qi stagnation, etiology, pathogenesis and clinical syndromes in TCM, Meta-analysis results, and evaluation strategy of establishing an animal model combining disease and syndrome in our laboratory, the biological surrogate outcomes suitable for the evaluation of animal models of AP with syndrome of liver depression and Qi stagnation were extracted then. The chronic unpredictable stress(CUS) method and chronic unpredictable stress +L-arginine(CUS +L-Arg) method were used to construct the rat model, and the above biological surrogate outcomes were used to evaluate whether an AP rat model was established. During the experiment, the weight and syndrome scores of the rats were observed and recorded. At the end of the experiment, the rats' serum, organs and tissues were collected from the operation to detect the various indicators. As compared with the normal group, the syndrome scores of the CUS group and CUS +L-Arg group were significantly increased(P<0.01); the anti-syndrome medicine Chaihu Shugan Pills could significantly reduce the syndrome scores of the two groups of rats(P<0.01), indicating that both modeling methods can replicate the syndrome of liver depression and Qi stagnation in the rat model. As compared with the normal group, the serum amylase(AMY) activity level was increased by 3 times in the CUS +L-Arg group(P<0.01), and the AMY activity level was also increased in CUS group, but not up to 3 times of the normal value. As compared with the normal group, the le-vels of TNF-α and IL-6 mRNA in the pancreatic tissues of the CUS +L-Arg group were significantly increased(P<0.01); the levels of TNF-α mRNA in the pancreatic tissues of the CUS group were significantly increased(P<0.05), but IL-6 mRNA level only showed a rising trend, indicating that only the CUS + L-Arg method can be used to replicate the AP damage in the disease-syndrome combination model. The CUS + L-Arg method can be used for continuous modeling for 4 weeks to establish a disease-syndrome combination model of AP rats with syndrome of liver depression and Qi stagnation. The model has the characteristics of repeatability, stability after mode-ling, low animal mortality, and similar clinical pathogenesis. It can be used for the evaluation of traditional Chinese medicine efficacy and the verification of efficacy network.

Effect of Xiaoyaosan on sexual behavior and inflammatory factors of rat with depression / 国际中医中药杂志

Objective@#To study the effects of Xiaoyaosan on sexual behavior and inflammatory factors of rat with depression.@*Methods@#The establishing depressive rat models of chronic mild unpredictable stress were established. The rats were randomly divided into model group and Xiaoyaosan group, 15 in each group. The Xiaoyaosan group was given 4.612 5 g/(kg•d) Xiaoyaosan, the blank group and the model group were intragastrically administered with normal saline once daily. After 4 weeks of oral administration, mount frequency and perineal licking numbers to female rats in each experimental group were observed by sexual behavior experiment, and the spleen index and thymus index were calculated. The serum DA, IL-1β, IL-6 levels were tested by Elisa.@*Results@#Compared with the normal group, the mount frequency (4.42 ± 3.91 vs. 11.58 ± 6.54), perineal licking numbers (3.53 ± 3.29 vs. 16.36 ± 10.68) and serum DA levels (14.14 ± 0.71 pg/ml vs. 17.44 ± 4.06 pg/ml) in the model group significantly decreased (P<0.05 or P<0.01), and the thymus index (0.012 4 ± 0.001 8 vs. 0.009 3 ± 0.001 7), serum IL-1β (39.45 ± 11.98 pg/ml vs. 28.62 ± 6.61 pg/ml), IL-6 levels (9.74 ± 1.49 pg/ml vs. 6.40 ± 0.66 pg/ml) significantly increased (P<0.05 or P<0.01). Compared with the model group, the contents of serum DA in Xiaoyaosan group (15.90 ± 1.24 pg/ml vs. 14.14 ± 0.71 pg/ml) increased significantly (P<0.01), and the thymus index (0.009 9 ± 0.001 3 vs. 0.012 4 ± 0.001 8) and IL-6 levels (8.32 ± 0.39 pg/ml vs. 9.74 ± 1.49 pg/ml) decreased significantly (P<0.05).@*Conclusions@#The Xiaoyaosan had a therapeutic effect on immune dysfunction and increases the expression of serum dopamine in depressive rats, which may be one of the mechanisms of its anti-depression.

Effects of vagus nerve stimulation on inflammatory factors and apoptosis in depression model rats / 中华行为医学与脑科学杂志

Objective To explore the influence of vagus nerve stimulation (VNS) on inflammatory factors in serum and nucleus of the solitary tract,and hippocampal apoptosis in rats with depression induced by chronic unpredictable stress ( CUS). Methods Totally 32 male Sprague Dawley ( SD) rats aged 8-9 weeks were selected. Eight rats were chosen as control group,and the other 24 rats were treated as the de-pression model with CUS. The rats were randomly divided into CUS,fluoxetine and VNS group,with 8 rats in each group after successful modeling. The control group and CUS group were induced by normal saline. Flu-oxetine group and VNS group were implanted with VNS stimulation electrode. The VNS stimulation lasted for 28 d. On the time points of before experiment,after modeling and after treatment,the sucrose consumption test and open-field test (OFT) were performed to observe the behavioral changes of rats. Elisa was used to detect the levels of TNF-α,IL-6 and IL-1β in serum and nucleus of the solitary tract. Cell apoptosis was ob-served with TUNEL staining in hippocampal CA1 region. Results ( 1) Sucrose consumption experiment and OFT showed that,compared with the CUS group,the consumption of sucrose,percentage of sucrose con-sumption,scores of vertical and horizontal movement increased significantly in the VNS group ( consumption of sucrose: (11. 78±2. 67) ml,(8. 06±2. 85) ml; percentage of sucrose consumption: (72. 31±9. 98)%, (63. 67±8. 95)%; score of vertical movement: (16. 61±3. 98),(10. 31±3. 86); score of horizontal move-ment: (44. 25±9. 59),(36. 21±7. 21)) (t=4. 87,7. 98,5. 87,9. 12,all P<0. 05). There was no signifi-cant difference between VNS and fluoxetine groups (consumption of sucrose: (11. 32±2. 66) ml; percentage of sucrose consumption: (71. 31±9. 03)%; score of vertical movement: (15. 63±4. 11); score of horizontal movement: (45. 61±8. 54)) (t=-0. 32,-1. 83,0. 98,-1. 13,all P>0. 05). (2) Compared with the CUS group,levels of TNF-α,IL-6 and IL-1β in serum decreased in the VNS group ( serum TNF-α: ( 46. 72 ± 11. 63) pg/ml,(125. 47±15. 18) pg/ml; serum IL-6: (243. 65±38. 90) pg/ml,(441. 39±83. 31) pg/ml;serum IL-1β: (209. 31±32. 45) pg/ml,(339. 21±76. 37) pg/ml) (t=-70. 38,-196. 25,-131. 13,all P<0. 05). The results in the VNS group were lower than those in the fluoxetine group (serum TNF-α: (58. 76 ±12. 64) pg/ml; serum IL-6: (308. 83± 64. 31) pg /ml,serum IL-1β: ( 249. 18 ± 43. 6) pg/ml) ( t=-15. 38,-64. 25,-18. 83,both P<0. 05). The levels of TNF-α,IL-6 and IL-1β in nucleus of the solitary tract in the VNS group were lower than those in the CUS ( TNF-α: (53. 52± 12. 31) pg/ml,(135. 51± 20. 64)pg/ml; IL-6: (265. 31±45. 63) pg/ml,(465. 32±60. 21) pg/ml; IL-1β: (212. 66±43. 32)pg/ml, (365. 96±76. 32) pg/ml) (t=-79. 38,-189. 13,-127. 50,all P<0. 05) and fluoxetine groups (TNF-α:(63. 42±10. 64) pg/ml; IL-6: (315. 62±53. 21) pg/ml; IL-1β: (278. 32±65. 38) pg/ml ) (t=-10. 25,-39. 00,-83. 00,all P<0. 05). (3) The apoptotic rate of hippocampal CA1 region in VNS group ((21. 41± 5. 86)%) was lower than that in the CUS group ((32. 78±8. 32)%) (t=-10. 75,P<0. 05); and there was no difference between VNS group and fluoxetine group ((22. 54±6. 31)%) (t=-1. 75,P>0. 05). Conclu-sion VNS can improve the depression behavior in rats with depression induced by CUS and the mechanism maybe related to inhibiting the expression of TNF-α,IL-6 and IL-1β in serum and nucleus of the solitary tract and cell apoptosis in hippocampal CA1 region.

Antidepressant effects of Jiaotai Pills based on NO-cGMP signal transduction pathway in chronic mild unpredictable stress depression rats / 中草药

Objective To investigate the effect of Jiaotai Pills on antidepressants in chronic mildly unpredictable stress (CUMS) depression model rats based on nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signal transduction pathway. Methods The depression model of rats was induced by CUMS. On day 21 of the experiment, the rats in each group were treated with continuous ig administration for 14 d. The concentrations of NO and cGMP in hippocampus and plasma of rats were detected by Elisa method. The mRNA expression of NO synthase (including iNOS and nNOS) and NMDA receptor subunits NR1, NR2A, and NR2B in rat hippocampus was detected by RT-PCR. Results Compared with the control group, the levels of NO and cGMP in the hippocampus and plasma in the model group were significantly increased. The expressions of iNOS mRNA, nNOS mRNA, NR1 mRNA, NR2A mRNA, and NR2B mRNA in the hippocampus were significantly increased in the model group. Compared with the model group, Jiaotai Pills high, medium, and low dose and positive drug administration reversed the above changes. Conclusion Jiaotai Pills have the antidepressant effect on depression rats with CUMS by regulating NO-cGMP signal transduction pathway.

Effects of maternal deprivation on stress response and efficacy of escitalopram in adult rats / 中华行为医学与脑科学杂志

Objective To investigate the effects of maternal deprivation on chronic stress?induced depression behavior and its characteristics in adult rats,and to evaluate the effects of maternal deprivation on the efficacy of escitalopram. Methods Newborn SD male rats were randomly divided into control ( C ) group,maternal deprivation (MD) group,chronic unpredictable stress (CUPS) group,maternal deprivation and chronic unpredictable stress ( MD+CUPS) group. Rats in control group received no experimental han?dling.Rats in MD group and MD+CUPS group received maternal deprivation from the lst day after birth for 14 days.Rats in CUPS group and MD+CUPS group received chronic unpredictable stress from 10 th weeks after birth for 28 days. Screened the rats with depression behaviors and treated them with escitalopram for 4 weeks. Results The incidence of anhedonia was significantly different among 4 groups (χ2=143.24, PCUPS group (40.98%) > MD group (17.11%) >C group (4.17%), P<0.0083). The incidence of behav?ioral despair was significantly different among 4 groups (χ2=70.34, P<0.05). Pairwise comparison showed the incidence of behavioral despair in MD+CUPS group (43.43%) and CUPS group (39.34%) were signifi?cantly higher than that in MD group (13.51%) and C group (3.33%),but no difference was observed be?tween MD+CUPS and CUPS group (P<0.0083) . The incidence of behavioral despair in MD group was signif?icant higher than that in C group. There was no significant efficacy of escitalopram on anhedonia and behav?ioral despair among 3 stressed models. However the recovery incidence from anhedonia (44/140) was significantly lower than that from behavioral despair (76/140) (χ2=14.93, P<0.05). Conclusion The maternal deprivation in?creases the stress sensitivity and the incidences of anhedonia in adult rats.The efficacy of escitalopram on behavioral despair is higher than that on anhedonia without influence from maternal deprivation.

Effects of Jiaotai Pill on behavior and monoamine neurotransmitters of depression rat model / 中草药

Objective: To study the effects of Jiaotai Pill on the behavior and monoamine neurotransmitters of chronic mild unpredictable stress (CUMS) depression rat model and to investigate the anti-depression effect and mechanism of Jiaotai Pill. Methods: A total of 72 SD rats were divided into six groups randomly, namely control, model, positive drug (fluoxetine hydrochloride, 7.5 mg/kg), low-, mid-, and high-doses of Jiaotai Pill (crude drug 0.75, 1.5, and 3 g/kg) groups (n = 12), which were reared in cage and execpt the control group, the other five groups of rats were given CUMS to stimulate the production of CUMS depression model, then ig given Jiaotai Pill for 14 d. Rats in each group were measured the body weight and the rate of sucrose preference once a week to observe the open-field activity behavior (through the horizontal grid and the number of vertical changes) at the 5th week. All the animals were killed to get the blood and brain cortex to test the levels of NE, 5-HT, and 5-HIAA in hippocampus, cortex, and hypothalamus by high performance liquid chromatography (HPLC). Results: Compared with the model group, the test indexes of rat body weight, sucrose water consumption, and the open-field activity behavior were significantly increased in the low-, mid-, and high-dose of Jiaotai Pill groups. And the contents of NE and 5-HT increased, while the content of 5-HIAA decreased obviously in the hippocampus, cortex, and hypothalamus in all Jiaotai Pill groups (P < 0.05 or 0.01). Conclusion: Jiaotai Pill has a better antidepressant effect whose mechanism is related to increasing the level of monoamine neurotransmitters in the cerebral cortex.

Effects of Different Processes ofBaijin Capsule on Treatment of Mice with Chronic / 中国中医药信息杂志

Objective To evaluate the efficacy of different processes ofBaijin Capsule to treatment of mice with chronic unpredictable stress-induced depression.Methods Chronic unpredictable stress was used to establish depression mice models. Experimental mice were divided into the following groups according to body mass: model group, positive medicine group, artware one (traditional process) high-dose and low-dose groups, and artware (refining process) two high-dose and low-dose groups. All medication groups were given relevant medicine for gavage. By detecting the two behavior indexes, immobility time of swimming and tail suspension of mice, the anti-depression effects of traditional process and refining process ofBaijin Capsule were investigated. By detecting autonomic activities and body mass, tested medicine was examined for function state of central excitation and changing animal body.Results The times for automatic activities ofBaijin Capsule in the model and artware (refining process) two high-dose and low-dose groups were (138.27±40.70)s, (100.01±34.75)s and (88.15±30.62)s, respectively, with statistical significance (P<0.01); the mice swimming immobility times in the model and artware (refining process) two low-dose groups were 668±19 and 705±24, respectively, with statistical significance (P<0.01); the mice tail suspension immobility times in model and artware (traditional process) one high-dose groups group were (28.14±1.25)g and (26.43±2.58)g, respectively, with statistical significance (P<0.05); the mice tail suspension immobility times in model and artware (refining process) two high-dose groups were (98.29±36.90)s and (87.54±30.05)s. Mice tail suspension immobility time in artware (refining process) two high-dose group decreased,without statistical significance.Conclusion Refining process ofBaijin Capsule can effectively be used to treat mice with chronic unpredictable stress-induced depression, and the efficacy is superior to the traditional process.

Salivary cortisol response to electrical stimulation in TMD cases and its relation with pain catastrophizing / 实用口腔医学杂志

Objective:To analyse the salivary cortisol changes in patients with temporomandibular disorders(TMD)after electrical stimulation,and the relationship between cortisol and pain catastrophizing.Methods:1 1 TMD and 1 1 healthy subjects were evoked by electrical stimulation.The saliva samples were collested before test,50 s and 1 00 s of stimulation after test seperately.Salivary cortisol was analysed by ELISA kit.The pain catastrophizing scale(PCS)was answered by all the subjects before stimulation.Data were statis-tically analysed.Results:The salivary cortisol concentration in TMD patients was higher than that in the controls(P <0.05).After stimulation,it showed a downward trend.No interaction between time and groups.The total scores of PCS including three indexes(ru-mination,magnification,helpless)were positively correlated with salivary cortisol concentration.Conclusion:The unpredictable stress causes high level of cortisol.which is related to pain catastrophizing.

Effects of ceftriaxone on depressive-like behavior and changes of hippocampal glutamate transporter-1 in depression model C57 mice / 中华行为医学与脑科学杂志

Objective To investigate the effects of ceftriaxone on depressive-like behavior and changes of hippocampal glutamate transporter-1 (GLT-1) in C57 mice depression model,and to further explore the molecular mechanism of ceftriaxone on antidepressant action.Methods Thirty male C57 mice were randomly divided into control group(group A,n=10),CUS group(group B,n=10) and CUS+ceftriaxone group(group C,n=10).The mice of the CUS group and the CUS+ceftriaxone group were subjected to chronic unpredictable stress (CUS) for 2 sessions per day for 21 days.Then,the mice of the CUS+ceftriaxone group were given ceftriaxone for 21 days.Behavioral changes were assessed by the sucrose preference test and open field test.The GLT-1 protein levels in the hippocampus were detected by Western blot analysis at the end of the ceftriaxone treatment.Results (1) Compared with the control group,the percentage of sucrose preference,the total traveled distance,the moved velocity,and the frequencies of rearing of the CUS group were significantly decreased(P＜0.05) at the 21 days.However,the percentage of sucrose preference ((78.74 ± 3.54) ％),the total traveled distance ((6818.35 ± 505.14) cm),the moved velocity((12.36±0.89) cm/s),and the frequencies of rearing(58.20±4.05) of the CUS+ceftriaxone group at the end of the ceftriaxone treatment were improved significantly compared with the CUS group ((59.46 ± 2.75) ％,(2931.71±271.89) cm,(5.84±0.42) cm/s,(26.20±2.62),P＜0.05).(2) Western blot analysis indicated significant reductions of the GLT-1 protein levels in the hippocampus of CUS group (versus the control mice:P ＜0.05),and chronic ceftriaxone treatment reversed the CUS-induced decrease in the GLT-1 levels(P＜0.05).Conclusion Ceftriaxone might significantly improve depressive-like behavior in C57 mice depression model.Chronic unpredictable stress (CUS) could down-regulate the GLT-1 protein levels in the hippocampus,which are reversed by ceftriaxone.These results further support the notion enhanced expression of the GLT-1 protcin can be molecular mechanism of ceftriaxone on antidepressant action.

Effects of fluoxetine on changes of GLT-1 in rat prefrontal cortex after chronic unpredictable stress / 中国药理学通报

Aim To investigate the effects of fluoxe-tine on the changes of of protein levels of GLT-1 in pre-frontal cortex in rat depression model, and to further explore the molecular mechanism of antidepressant ac-tion of fluoxetine. Methods Sixty male SD rats were randomly assigned into three groups: control group, chronic unpredictable stress ( CUS) group, and CUS+fluoxetine group. The rats of CUS group and CUS+flu-oxetine group were subjected to CUS for 2 sessions per day for 35 days. Then, the rats of the CUS+fluoxetine group were given fluoxetine for 28 days. Behavioral changes were assessed by the sucrose preference and open field tests. The GLT-1 protein levels in the pre-frontal cortex were detected by immunohistochemistry and Western blot analysis at the end of the fluoxetine treatment. Results ( 1 ) Compared with the control group,sucrose preference, total traveling distance, ve-locity and frequencies of rearing were reduced in the CUS group ( P < 0. 01 ) . These behavioral changes could be reversed after 28 day fluoxetine treatment. (2 ) Immunohistochemistry assay indicated weak im-munoreactivity for GLT-1 in the prefrontal cortex of CUS group ( versus the control rats: P <0. 01 ); the immunoreactivity for GLT-1 of the fluoxetine-treated rats was significantly up-regulated compared with the CUS group rats ( P<0. 01 ) . ( 3 ) Western blot analy-sis indicated significant reductions of GLT-1 in the pre-frontal cortex of CUS group ( versus the control rats:P<0. 01 ) , and chronic fluoxetine treatment reversed the CUS-induced decrease in GLT-1 levels ( P <0. 01 ) . Conclusions Chronic unpredictable stress ( CUS ) could down-regulate the GLT-1 protein levels in the prefrontal cortex, which is reversed by fluoxe-tine. These results further support the notion that en-hanced expression of the GLT-1 protein could be mo-lecular mechanism of fluoxetine antidepressant effect.

Effects of yohimbine on norepinephrine release by locus coeruleus in stressed rats / 中华行为医学与脑科学杂志

Objective To study the cellular and molecular modulation mechanisms of norepinephrine (NE) release in hypothalamus induced by electrical stimulation in locus coeruleus (LC) in the rat model of depression-like behavior.Methods The depression-like behavior model was established by combining separation and chronic unpredictable stress stimulations.After the model establishment,behavior tests were used to verify the success of modeling.NE release in the hypothalamus induced by electrical stimulation in LC was studied in real time and NE signal was recorded with carbon fiber electrode.The peak value,the time to peak and half-life period of NE signal in both group rats were measured and analysed.Results The bodyweight,score of open-field test,percentage of sucrose preference of model group rats ((263.9± 16.4) g,(19.4±7.9),(44.3± 10.8) ％) were significantly lower than those((314.3±24.3) g,(53.3± 19.0),(60.6± 13.3) ％) of control group(P＜0.01).The peak value of NE signal in the hypothalamus induced by electrical stimulation in locus coeruleus in depression-like behavior model rats((176.9±50.4) pA)was less than that((361.6±88.6) pA)in control group(P＜0.01),and the time to peak of NE signal was also shortened in depression-like behavior model group rats (P＜0.05).Intraperitoneal injection of yohimbine (3 mg/kg) potentiated electrical stimulation induced NE release in depression-like behavior model rats but not in control group.Conclusion The chronic unpredictable stresses attenuate the secretion of NE in the hypothalamus induced by electrical stimulation in LC in rats.Yohimbine,a presynaptic α2 receptor antagonist,increased NE release in hypothalamus in depression-like behavior model rats.These findings suggest that the LC projects functionally to the hypothalamus and the projection may contribute to the pathogenesis of depression.

Chronic Administration of Bacopa Monniera Increases BDNF Protein and mRNA Expressions: A Study in Chronic Unpredictable Stress Induced Animal Model of Depression

OBJECTIVE: The present study aimed to investigate whether graded doses of Bacopa Monniera (BM) extract could produce antidepressant-like effects in chronic unpredictable stress (CUS) induced depression in rats and its possible mechanism(s). METHODS: Rats were subjected to an experimental setting of CUS. The effect of BM extract treatment in CUS-induced depression was examined using behavioral tests including the sucrose consumption, open field test and shuttle box escape test. The mechanism underlying the antidepressant-like action of BM extract was examined by measuring brain-derived neurotrophic factor (BDNF) protein and mRNA expression in brain tissues of CUS-exposed rats. RESULTS: Exposure to CUS for 4 weeks caused depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity and escape latency. In addition, it was found that BDNF protein and mRNA levels in the hippocampus and frontal cortex were lower in CUS-treated rats, as compared to controls. Daily administration of the graded doses of BM extract during the 4-week period of CUS significantly suppressed behavioral changes and attenuated the CUS-induced decrease in BDNF protein and mRNA levels in the hippocampus and frontal cortex. CONCLUSION: The results suggest that BM extract alleviates depression induced by CUS. Present study also confirms that 80-120 mg/kg doses of BM extract have significantly higher antidepressant-like activity.

Effect of chronic and unpredictable pre-gestational stress on the brain-derived neurotrophic factor-tyrosine protein kinase B signal transduction pathway in the brain of the offspring rats / 中华实用儿科临床杂志

Objective To investigate the effect of chronic and unpredictable pre-gestational stress on the serum cortisol level of the offspring,as well as the expressions of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB) in hippocampus when they were 2 month old.Methods Adult female SD rats were divided randomly into 2 groups:the control group and the chronic unpredictable stress (CUS) model group.All rats were tested in the open field test and sucrose intake test before and after CUS protocol.All offspring rats were sacrificed when 2-month old.Serum cortisol (COR) levels were determined by using a standard radioimmunoassay kit.The expressions of BDNF and TrkB in hippocampus were studied by immunoreactivity quantitative analysis.Results 1.After CUS procedure,CUS group showed decreasing activities in the open field test and decreasing sucrose consumption in sucrose intake test compared to the control group and before CUS procedure.2.The serum COR levels in the female offspring rats of CUS group (128.9 ± 7.3) μg/L were higher than those of the control group (119.9 ± 9.0) μg/L,as well as the male offspring of CUS group(116.5 ± 10.9) μg/L compared with the control group(105.4 ± 10.4) μg/L,but the body weight and brain weight between the offspring of 2 groups were not statistic significance.3.Immunoreactivity quantitative analysis showed that the gray values of BDNF in the female offspring of CUS group (36.1 ± 8.5) decreased compared with the control group(42.4 ± 6.9),as well as the male offspring of CUS(39.6 ± 8.4)compared with the control group (43.7 ± 6.4).4.The gray values of TrkB in the female offspring of CUS group (47.1 ± 2.9) decreased than the control group(50.2 ± 3.9),as well as the male offspring of CUS (46.5 ± 6.7)compared with control group(50.5 ± 5.4).Conclusion Pre-gestational stress reduced the expressions of BDNF and TrkB in hippocampus of the offspring which may relate to hypothalamic pituitary adrenal.

Pinching spine: A potential treatment for depression / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether pinching spine (PS, i.e. , a traditional Chinese manipulative therapy) is beneficial to ameliorating the depressive state (including behavioral deficit, retardative weight gain and decreased sucrose consumption) in a rat model of depression induced by chronic unpredictable stress (CUS) and to explore the candidate mechanism of action.</p><p><b>METHODS</b>PS was performed on rats' spine once daily for 1 week after exposure to CUS. The open-field test, body weight measuring, and sucrose intake test were applied on different dates: before stress (d0), at the end of stress (d21) and after PS treatment (d28), respectively. Then the rats' hippocampuses were performed genome-wide microarray analysis, and the expression levels of several genes were evaluated by real-time polymerase chain reaction (PCR).</p><p><b>RESULTS</b>Exposure to CUS resulted in decreases of behavioral activity and sucrose consumption, which were reversed significantly after PS treatment. The expression of several genes relevant to energy metabolism, anti-oxidation, and olfactory receptor, etc., were down-regulated, while the expression of those relevant to hemostasis, immunity-inflammation, and restriction of activities and ingestion, etc., were up-regulated in hippocampuses of rats exposed to CUS. PS treatment significantly inverted these changes. Furthermore, increase or decrease in gene expression evaluated by realtime PCR was concordant with up-regulated or down-regulated expression evaluated by microarray analysis.</p><p><b>CONCLUSION</b>PS showed a potential antidepressant-like effect, of which the action mechanism might be due to gene expression regulation in hippocampus.</p>

The effects of quetiapine on the improvement of behavior and expression of pERK1/2 in the hippocampus of chronic unpredictable stress model rats / 中华行为医学与脑科学杂志

Objective To investigate the effect of quetiapine on the behavior and expression of pERK1/2 in chronic unpredictable stress(CUS) model rats.Methods 32 adult male Sprague Dawley rats were randomly divided into four groups (n =8 for each group):control group,CUS group,CUS + QUE (5 mg/kg,L) group and CUS + QUE(10 mg/kg,M)group.The rats in control group were left undisturbed in their home cage for 28 days and the other groups were exposed to 28 consecutive days of CUS,then the rats in control group and CUS group were treated with 1％ DMSO in saline (5 ml/kg,intraperitoneal injection),the rats in CUS + QUE (L)group and CUS + QUE(M) group respectively treated with quetiapine (5 mg/kg)or quetiapine(10 mg/kg) for consecutive 7 days.The weight data of each group were recorded,and the behavioral changes in these rats were analyzed by open field test and forced swimming test;and the expression of pERK1/2 was measured by Western blot.Results (1)Compared with control group,quetiapine (10 mg/kg) ameliorated the inhibition of body weight gain that induced by chronic unpredictable stress (P ＜ 0.05),but quetiapine (5 mg/kg) did not have this effect.(2)Open field and Forced swimming test showed significant difference (P ＜ 0.05) of horizontal motion distance (F =17.846),the number of central region entering(F=4.720) and the immobility time(F=26.090) in each group.And these tests showed that horizontal motion distance and the number of central region entering in CUS group ((6696.30 ±1061.19)mm,(19.63 ±9.15)times) were significantly lower than that of control group ((10824.61 ± 1399.37) mm,(37.75 ± 13.02) times) and CUS + QUE (M) group ((9637.51 ± 1630.16) mm,(32.38 ± 6.23)),while the immobility time (110.73 ± 15.98)s were significantly higher than that of control group((66.13 ± 5.18)s)and CUS + QUE (M) group((73.40 ± 11.99) s,P ＜ 0.05).But there was no significant difference between that of CUS group and CUS + QUE(L) group(P＞0.05).(3)The expression of pERK1/2 in CUS group showed significant decrease when compared with control group or CUS + QUE (M) group,but showed no significant difference with CUS + QUE(L) group(F=6.641,P＜ 0.01).Conclusion Quetiapine can ameliorate depressive-like behaviors induced by chronic unpredictable stress,and this effect may be carried out by up-regulation the expression of pERK1/2 in the hippocampus.

Mechanisms of serotonin transporter and serotonin 1A receptor in the different susceptibility of chronic unpredictable stress / 中华行为医学与脑科学杂志

Objective To investigate the expression of serotonin transporter (5-HTT) and serotonin 1A treceptor (5-HT1 A R) located in the chronic unpredictable stress (CUS)-relative brain areas (mPFC,VTA,NAc) in high and low CUS susceptibility rats,thus to unveil the possible mechanism lead to the different CUS susceptibility.Methods One hundred and fifty male Sprague-Dawley rats were randomly assigned into experiment group (n =120) and control group (n =30).Rats in experiment group were trained according to established CUS procedure.OFT and FST were used to assess the different susceptibility to CUS:high susceptibility group (H group)and low susceptibility group (L group).After the model was established,rats were scarified and cardio-perfused,and the brains were removed and sliced up coronarily.The sections including ventral tegmental area (VTA),nucleus accumben (NAc),medial prefrontal cortex (mPFC) were selected.The mRNA levels of 5-HTT and 5-HT1AR in the regions were estimated with in situ hybridization.Results The expression of 5-HTT in H group were significantly lower than that of in the control and L group in all regions (mPFC:169.20 ± 8.23 vs 143.53 ±5.31 ; Nac:177.41 ± 5.68 vs 158.65 ± 5.24 ; VTA:174.16 ± 5.61 vs 158.65 ± 4.85),and the difference between the H and L group was significant(P＜0.01) ;however,the expression of 5-HT1AR in H group were significantly higher than that of in the control and L group in all regions (mPFC:113.98 ± 7.46 vs 125.90 ± 3.30 ; Nac:112.11± 5.50 vs 125.06 ± 3.97 ;VTA:103.11 ± 6.05 vs 115.57 ± 3.19),and the difference between the H and L group was significant (P＜ 0.01).Conclusion The overexpression of 5-HT1AR and down regulation of 5-HTT in the circuit of VTA-NAc-mPFC may be the basis of the high susceptibility to CUS.

Effects of maternal rats exposed to chronic unpredictable stress before pregnancy on the postpartum behavior and neurobiology of themselves and their progency / 中华行为医学与脑科学杂志

Objective To determine the effects of maternal rats exposed to chronic unpredictable stress before pregnancy on the behavior and neurobiology of the mother and their offspring.Methods Two-month Virgin female Sprague-Dawley(SD) rats were applied to study.Females were housed with sexually experienced males (ratio 3:1) for propagation after 21-day chronic unpredictable stress.The behaviors of rats and their two-month-offspring were tested.The two-month rats were injected intraperitoneally with BrdU,then the brains were removed and 20 μm frozen sections were used to detect the neurogenesis of hippocampus.Results 1.Open field test:after lactation,CUS + Pre group ((720.52 ± 238.99) cm),CUS group ((995.62 ± 191.77) cm),CON group ((464.95 ±210.11)cm) and CON + Pre group((740.76 ± 281.48)cm) had statistic difference in total distance(P ＜ 0.05).The total distance((1281.10 ±247.89)cm) and border distance((1153.20 ±238.19)cm) in female two-monthprogeny were higher than these in male two-month-progeny ((1074.70 ± 263.35) cm,(957.28 ± 82.94) cm) in CUS + Pre group (P ＜ 0.05).2.Sucrose consumption test:after lactation,the sucrose intake ((13.00 ± 3.46) g)and sucrose consumption percentage((87.00 ±9.01)％) in CUS + Pre group were higher than that in CUS group ((8.13 ± 3.36) g,(79.06 ± 6.45) ％,P ＜ 0.05).The sucrose intake ((12.43 ± 3.31) g) and sucrose consumption percentage((86.90 ± 5.80)％) in CON group were higher than that in CUS group ((8.13 ± 3.36) g,(79.06 ± 6.45) ％,P ＜ 0.05).The sucrose intake ((14.71 ± 4.39) g) and sucrose consumption percentage ((91.54 ± 1.89) ％) in CON + Pre group were significantly higher than those in CUS group ((8.13 ± 3.36) g,(79.06 ± 6.45) ％) (P ＜ 0.01).3.Immunohistochemistry:there was no statistic difference on the new neuron in dentate gyrus of hippocampus in both female and male two-month-progeny of CUS group and CON group((1.18 ±0.37) cells,(1.24 ± 0.41) cells,(1.38 ± 0.47) cells,(1.41 ± 0.35) cells) (P ＞ 0.05).Conclusion The 21d CUS before pregnancy induce the anxiety-like behavior and depressive-like behavior in maternal rats,and lactation can attenuate influence of stress to protect maternal rats.There is no effect on the behavior and cell proliferation of hippocampus in adult progeny by chronic unpredictable stress exposure before pregnancy.However,there is the difference of anxiety-like behavior in both female and male two-month-progeny.

The effects of daylily on the behaviors and learning memory in the depressed rats / 中华行为医学与脑科学杂志

Objective To observe the effects of the extract from daylily on the learning and memory in depression model rats, and to explore its possible mechanism. Methods Rats were randomly divided into control group, model group ( CUMS), the positive group (CUMS + fluoxetine) , high, medium and low dose group (stress + daylily extract in different doses), 12 rats in each group. The depression model was established by combining separation and chronic unpredictable stress. Body mass, open-field-test and sugar consumption experiment were used to evaluate the changes of behaviors in rats. And morris water Maze test was used to evaluate the ability of learning and memory. Results There was no statistically distinction between the rats of each group on weight and the behavioral indicator before modeling. Compared with the control group, the vertical movement,horizontal movement of open box test in the model group were reduced (P＜0.05 ) ,and sugar consumption and preference degree decreased (P<0.05 ).The target quadrant time, platform resident time, effective area residence time and crossing platform times in the water maze test of the model group was less than those of the control group. The daylily effect was evaluated at 0, 7, 14, 21, 28, 35, 42 days respectively post treatment. There were significant differences in depression behaviors between model group and daylily group(P＜0.05). And each indicator in the water maze test of the daylily group (high, medium dose) was more than that of model group (P ＜ 0. 05). Control group, model group, positive group, high, medium and low dose group, vertical movement scores were (41.83 ± 17.63; 8.14 ±4.23; 12.73 ±7.21; 23.17 ± 18.75; 8.38 ±3.46; 13.50 ±5.44); horizontal movement scores were (69.92 ±34.04; 28.33 ±20.36; 62.25 ± 15.72; 69.42 ±35.17 ; 49.08 ±32.85; 48.08 ±21.19). Conclusion Daylily may be partially work on the depression of rats, with some antidepressant effect, meantime,daylily can improve the ability of learning and memorizing of the depressed rats.