急性缺血性脑卒中睡眠障碍与5–HT、Hypocretin的相关性研究

目的:研究急性缺血性脑卒中睡眠障碍与5–羟色胺(5–HT)、下丘脑外侧区分泌素(Hypocretin)的相关性,为急性缺血性脑卒中患者睡眠障碍的发病机制研究和病情评估提供依据。方法:选择2018年10月至2019年12月于南华大学附属第二医院进行治疗的100例急性缺血性脑卒中睡眠障碍患者作为观察组。选取同期在本院进行体检的无心脑血管疾病的50例健康者作为对照组。比较两组研究对象的匹兹堡睡眠质量指数问卷(PSQI)评分,并分析其与5–HT、Hypocretin水平的相关性。结果:观察组患者的PSQI评分、5–HT水平明显高于对照组,Hypocretin水平明显低于对照组,组间比较,差异具有统计学意义(P<0.05)。多重线性回归分析结果显示,5–HT、Hypocretin水平为观察组患者出现睡眠障碍的相关因素,5–HT水平与PSQI评分正相关,Hypocretin水平与PSQI评分负相关。结论:急性缺血性脑卒中患者睡眠障碍程度与血清5–HT、Hypocretin有关,其水平变化可反映病情严重程度。

Augmentative effect of tetrandrine on pentobarbital hypnosis mediated by 5-HT_(1A) and 5-HT_(2A/2C) receptors in mice

It has been reported that augmentative effect of tetrandrine on pentobarbital hypnosis in mice may be related to serotonergic system. The present study was undertaken to investigate the interaction of tetrandrine and different 5-HT receptors on pentobarbital-induced sleep by using the loss-of-righting reflex method. The results showed that augmentative effect of tetrandrine on pentobarbital hypnosis in mice were potentiated by the p-MPPI （5-HT1A receptor antagonist） （1 mg/kg, i.p.） and ketanserin （5-HT2A/2C receptor antagonist） （1.5 mg/kg, i.p.）, respectively. Pretreatment with either 8-OH-DPAT （5-HT1A receptor agonist） （0.1 mg/kg, s.c.） or DOI （5-HT2A/2C receptor agonist） （0.2 mg/kg, i.p.） significantly decreased pentobarbital-induced sleep time, and tetrandrine （60 mg/kg, i.g.） significantly reversed this effect. These results suggest that both the 5-HTLA and 5-HT2A/2C subfamily may be involved in the potentiating mechanism of tetrandrine＇s effects on pantobarbital hypnosis.

大豆黄酮对衰老小鼠脑组织神经递质含量的调节

研究大豆黄酮对D–半乳糖致衰老小鼠脑神经递质水平的调节.连续背部注射D–半乳糖6周,建立衰老模型,然后灌胃大豆黄酮5周(实验组Ⅰ、Ⅱ的剂量分别为5、10 mg/(kg.d)),监测不同脑区乙酰胆碱、乙酰胆碱酯酶、多巴胺和5–羟色胺含量变化,探讨大豆黄酮对衰老小鼠脑组织神经递质水平的影响.结果表明,灌胃衰老小鼠大豆黄酮后,大脑皮质和海马中乙酰胆碱、乙酰胆碱酯酶、多巴胺和5–羟色胺含量明显上升,并且具有一定的剂量效应.说明大豆黄酮可以改善衰老小鼠脑组织中神经递质含量,具有明显的抗衰老作用.

Beneficial effects of moderate voluntary physical exercise and its biological mechanisms on brain health

This article reviewed the beneficial effects of moderate voluntary physical exercise on brain health according to the studies on humans and animals, which includes improving psychological status and cognitive function, enhancing psychological well-being, decreasing the risks of Alzheimer＇s disease （AD） and dementia, and promoting the effects of antidepressant and anxiolytic. The possible underlying neurobiological mechanisms are involved up-active and down-active pathways. The up-active pathway is associated with enhancements of several neurotransmitters systems afferent to hippocampus, including norepinephrine （NE）, serotonin （5-Hydroxytryptamine, 5-HT）, acetylcholine （ACh） and γ-aminobutyric acid （GABA）. The down-active pathway is mainly concerned with up-regulation of the brain-derived neurotrophic factor （BDNF） and neurogenesis. It is suggested that NE activation via β-adrenergic receptors may be essential for exercise-induced BDNF up-regulation. The possible intracellular signaling pathways of NE-mediated BDNF up-expression may be involved in GPCR-MAPK-PI-3K crosstalk and positive feedback.

Decreased expression of serotonin in the jejunum and increased numbers of mast cells in the terminal ileum in patients with irritable bowel syndrome

AIM: To investigate if there are changes in serotonin (5-HT) levels, enterochromaffin (EC) cells and mast cells in small intestinal mucosa of patients with irritable bowel syndrome (IBS). METHODS: Diarrhea-predominant (IBS-D, n = 20), or constipation-predominant (IBS-C, n = 18) IBS patients and healthy controls (n = 20) underwent colonoscopy and peroral small intestinal endoscopy, and mucosal samples were obtained at the descending part of the duodenum, proximal end of jejunum and terminal ileum. High-performance liquid chromatography- electrochemistry and immunohistochemical methods were used to detect 5-HT content, EC cells and mast cells. RESULTS: (1) There were no differences in the number and distribution of EC cells between IBS patients and the normal group. (2) The mucosal 5-HT contents at the duodenum, jejunum and ileum in IBS-C patients were 182 ± 90, 122 ± 54, 61 ± 35 ng/mg protein, respectively, which were all lower than those in the normal group (256 ± 84, 188 ± 91, and 93 ± 45 ng/ mg protein, respectively), with a significant difference at the jejunum (P < 0.05). There were no differences in the small intestinal mucosal 5-HT contents between IBS-D patients and the normal group. The mucosal 5-HT contents at the duodenum were significantly higher than those at the ileum in the three groups (P < 0.001). (3) The numbers of mast cells in patients with IBS-C and IBS-D at the ileum were 38.7 ± 9.4 and 35.8 ± 5.5/highpower field (hpf), respectively, which were significantly more than that in the normal group (29.8 ± 4.4/hpf) (P < 0.001). There was no significant difference in the numbers of mast cells at the other two parts between IBS patients and the normal group. The numbers of mast cells in IBS-C, IBS-D, and normal groups were all significantly higher at the ileum (38.7 ± 9.4, 35.8 ± 5.5, 29.8 ± 4.4/hpf, respectively) than at the duodenum (19.6 ± 4.7, 18.5 ± 6.3, 19.2 ± 3.3/hpf, respectively, P < 0.001). CONCLUSION: The changes in the 5-HT signaling pathway at the jejunum of IBS-C patients and the increase in mast cells in patients with IBS at the terminal ileum may offer evidence to explain the pathogenesis of IBS.

Protective effects of Zuogui Jiangtang Jieyu Formula on hippocampal neurons in rats of diabetes complicated with depression via the TRP/KYN metabolic pathway

Objective To explore the protective effects and mechanism of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZGJTJYF)on hippocampal neurons in rats of diabetes complicated with depression(DD)via the TRP/KYN metabolic pathway.Methods(i)In vivo experiments:60 specified pathogen free(SPF)grade male Sprague-Dawley(SD)rats were randomly divided into six groups with 10 rats in each groups:control,DD model,positive(1.8 mg/kg fluoxetine+0.18 g/kg metformin),high-dose ZGJTJYF(ZGJTJYFH,40.500 g/kg ZGJTJYF),middle-dose ZGJTJYF(ZGJTJYF-M,20.250 g/kg ZGJTJYF),and lowdose ZGJTJYF(ZGJTJYF-L,10.125 g/kg ZGJTJYF)groups.Except for the control group,other groups were established DD model by high-fat emulsion intake with single tail vein streptozotocin(STZ)and four weeks of chronic unpredictable mild stress(CUMS).All drug administration groups were treated by gavage during CUMS modeling,and the control and model groups were given equal amount of distilled water.After four weeks,the serum levels of blood glucose and glycosylated hemoglobin were measured to determine the hypoglycemic effect of ZGJTJYF.Moreover,the open field test and Morris water maze test were performed to evaluate the antidepressant effect of ZGJTJYF.Changes in 5-hydroxytryptamine(5-HT)level were detected via high-performance liquid chromatography with electrochemical detection(HPLC-ECD);the levels of tryptophan(TRP),kynurenine(KYN),and indoleamine 2,3-dioxygenase(IDO)in the hippocampus were detected using enzyme-linked immunosorbent assay(ELISA);the protein expression levels of synaptophysin(SYN)and postsynaptic density material-95(PSD-95)were detected via immunohistochemistry(IHC);and the protein expression levels of N-methyl-D-aspartate receptor(NR)2 A and NR2 B were detected using Western blot.(ii)In vitro experiments:five SPF grade SD pregnant rats(E16–18)were used to obtain primary hippocampal neurons(Ne),six SD new-born rats were used to collected primary astrocytes(As)and microglia(MG),and to establish a Ne-As-MG co-culture system.All co-culture systems were divided into six groups:control(PBS),model[150 mmol/L glucose+200μmol/L corticosterone(G&P)+PBS],blank(G&P+blank serum),positive(G&P+positive drug-containing serum),ZGJTJYF(G&P+ZGJTJYF serum),and 1-methyl-D-tryptophan(1-MT,IDO inhibitor)(G&P+1-MT)groups.After 18 h of intervention by corresponding treatment,immunofluorescence was used to analyze the protein expression levels of SYN,PSD-95,NR2 A,and NR2 B;ELISA was performed to measure the levels of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,and TRP/KYN metabolic pathway-related factors[TRP,KYN,kynurenine acid(KYNA),quinolinic acid(QUIN)].Results(i)In vivo experimental results showed that ZGJTJYF-M and ZGJTJYF-L significantly improved the elevated blood glucose state of DD rats(P<0.01 and P<0.05,respectively);ZGJTJYF-H,ZGJTJYF-M,and ZGJTJYF-L increased their autonomous activity,learning,and memory ability(P<0.01,P<0.01,and P<0.05,respectively).Moreover,the levels of 5-HT and TRP were significantly increased(P<0.01),and the levels of KYN and IDO were significantly decreased in the hippocampus(P<0.01)of rats after ZGJTJYF-M treatment.The protein expression levels of SYN and PSD-95 were significantly upregulated in hippocampal neurons(P<0.01),while the abnormal activation of NR2A and NR2B was markedly inhibited in hippocampus(P<0.05)of rats after ZGJTJYF-M treatment.(ii)In vitro experimental results showed that ZGJTJYF-containing serum significantly increased the protein expression levels of SYN and PSD-95 in hippocampal neurons(P<0.01),decreased the levels of IL-1β(P<0.01),IL-6(P<0.05),TNF-α(P<0.01),IDO(P<0.05),KYN(P<0.05),and QUIN(P<0.01),and increased the levels of TRP and KYNA(P<0.01)in the simulated DD state.ZGJTJYF also had an significantly inhibitory effect on the abnormal activation of NR2A and NR2B in neurons(P<0.05)in a stimulated DD state.Conclusion ZGJTJYF can effectively improve 5-HT deficiency in the hippocampus of rats by inhibiting IDO expression and regulating the TRP/KYN metabolic pathway,and it has a favorable protective effect on hippocampal neuron injury caused by DD.Therefore,ZGJTJYF is an effective potential therapeutic drug for the prevention and treatment of DD.

Venlafaxine Dependence： A Case Report

Venlafaxine, an SNRI （serotonin-norepinephrine reuptake inhibitor） drug, is commonly used to treat depression. Although it is very rare, venlafaxine may lead to addiction or abuse in some patients. To date, there are very limited data available on venlafaxine addiction. The aim of this article is to draw an attention to dependence of venlafaxine in clinical practice. Significant point of this article is： Our patient was addicted by ＂high＂ doses of venlafaxine for getting high effects. Overdose of venlafaxine produces an amphethamine-like ＂high＂ with experiences of euphoria by its ability to increase neurotransmitter levels in addiction literature [1-3]. We present a man aged 42 years, who was referred to our clinic for detoxification from venlafaxine addiction. He had been taking venlafaxine upto 1,950-2,100 mg/day to get high for the past 10 years. Physicians must be careful when prescribing antidepressants to patients, especially those with a history of alcohol and/or drug addictions or abuse.

Biogenic Amines Profile of Serbian Traditional Sausage in Relation to Raw Material and Production Conditions

Petrovska klobasa is a traditional dry fermented sausage produced in the Autonomous Province of Vojvodina. Formation of nine hiogenic amines was determined in three sausage groups produced from hot deboned （A1） and cold meat （B1, B3） during drying and ripening in traditional room （A1, B1） and in industrial ripening chamber （B3）. Dansyl chloride derived amines were analysed by high-performance liquid chromatography with diode-array detector （HPLC-DAD） on Eclipse XDB-C18 column. Histamine, the most important amine from food safety point of view, was not found in any of the analyzed samples. Serotonin and spermidine were also not detected in any samples, while spermin was determined in all analyzed samples. At the end of drying, phenylethylamine was the predominant amine in A1 sausage group （51.6 mg/kg）, and tryptamine in B1 （38.1 mg/kg） and B3 （28.7 mg/kg） sausage groups. At the end of ripening, tryptamine was the predominant biogenic amine in all sausage groups （133, 121 and 39.8 mg/kg in A1, B1 and B3 groups, respectively）. Total level of biogenic amines in all investigated sausages did not exceed 174 mg/kg at the end of drying and 238 mg/kg at the end of ripening period. Tryptamine and cadaverine may be used as indicators of total biogenic amines for sausages produced in traditional and indusrial conditions from hot deboned and cold meat.

Antinociceptive and Anti-inflammatory Activities of Methanol Extract of Ormosia coccinea （Aubl,） Jacks in vivo

The present study was conducted to evaluate the antinociceptive and anti-inflammatory activities of methanol extract of rachis of Ormosia coccinea （Aubl.） Jacks （MEOC） using animal models of nociception and inflammation. The antinociceptive activity of the extract was assessed using acetic acid-induced abdominal writhing, hot-plate, and formalin tests. Oral administration of MEOC （500 mg/kg） produced significant （t7 〈 0.05） antinociceptive effects when tested in mice using acetic acid-induced abdominal writhing test and on the inflammatory phase of the formalin test. It was also demonstrated that MEOC had no significant effect on the response latency time to the heat stimulus in the thermal model of the hot plate test. The anti-inflammatory activity of the extract was assessed using carrageenan, histamine and serotonin induced oedema in rat paw. The oral administration of MEOC showed maximum inhibition （64.29%） at 1 h on carrageenan edema, but it did not modify the edema induced by histamine and serotonin. The present results suggest that MEOC has a peripheral antinoeiceptive and anti-inflammatory action.

Effect of heat-sensitive moxibustion plus psychological intervention on SP, 5-HT and quality of life in patients with irritable bowel syndrome

Objective： To observe the effect of heat-sensitive moxibustion plus psychological intervention on serum contents of substance P（SP） and 5-hydroxytryptamine（5-HT）, as well as the quality of life（QOL） in patients with irritable bowel syndrome（IBS）. Methods： A total of 120 IBS patients were divided into three groups by random sampling method, 40 cases in each group. The heat-sensitive moxibustion group received heat-sensitive moxibustion, the psychological intervention group received psychological intervention, while the observation group received both methods. The therapeutic efficacy was evaluated after 3 courses of treatment. Results： After treatment, the therapeutic efficacy of the observation group was better than that of the heat-sensitive moxibustion group and the psychological intervention group（P〈0.01）, and the heat-sensitive moxibsution group was better than the psychological intervention group（P〈0.05）. In comparing the bowel symptom scale（BSS）, the observation group was better than the other two groups（P〈0.05）, and there was a significant difference between the heat-sensitive moxibustion group and the psychological intervention group（P〈0.05）. In the comparison of QOL, the observation group was significantly superior to the other two groups（P〈0.05）, and there was a significant difference between the heat-sensitive moxibustion group and psychological intervention group（P〈0.05）. In comparing serum SP and 5-HT, the observation group was markedly better than the other two groups（P〈0.05）, and there were significant differences between the heat-sensitive moxibustion group and psychological intervention group（P〈0.05）. The self-rating anxiety scale（SAS） and self-rating depression scale（SDS） were used to estimate the mental state of the three groups, revealing that the observation group was better than the heat-sensitive moxibustion group and the psychological intervention group（P〈0.05）, and there were significant differences between the latter two groups（P〈0.05）. Conclusion： Heat-sensitive moxibustion plus psychological intervention can regulate the levels of SP and 5-HT, improve BSS, SDS, SAS and QOL in treating IBS.

Experimentally investigating the effect of buccal acupuncture on analgesic time-effect characteristics and monoamine neurotransmitters

Objective： To investigate the analgesic time-effect characteristics and changes in concentrations of rabbit＇s hypothalamic 5-hydroxytryptamine （5-HT） and noradrenaline （NE） caused by buccal acupuncture in the rheumatoid arthritis （RA） rabbits, and to reveal the analgesic central mechanism of buccal acupuncture, thereby providing a theoretical basis for the treatment of pain by buccal acupuncture. Methods： Forty rabbits were randomly divided into a normal group, a model group, a body acupuncture group, and a buccal acupuncture group, with 10 rabbits in each group. No model was established in the normal group, while equal dose of normal saline was injected at the matched site and time point; rabbits in other groups were subjected to the establishment of RA models using egg protein. From the 27th day of the experiment, rabbits in each group received the designated intervention. Rabbits in the normal group and the model group were fixed for 30 min every day using the same method as those in the other groups. In the acupuncture group, Dubi （ST 35） and Zusanli （ST 36） on bilateral hind limbs were selected. Perpendicular needling （using the needles with 0.25 mm in diameter and 25 mm in length） was performed with twirling manipulation for 15 s at intervals of 5 min. The needles were retained for 30 min and acupuncture was performed once a day. In the buccal acupuncture group, the knee point in the buccal acupuncture and needles with a diameter of 0.25 mm and a length of 15 mm were selected. Oblique needling was performed with twirling manipulation for 15 s at intervals of 5 min. The needles were retained for 30 min and acupuncture was performed once a day. The thermal pain thresholds at the O, 5, 15, 30, 60, 120 and 240 rain after the 1st and 10th acupuncture therapy were measured with a PL-200 thermal-inducing pain meter. After the 10th acupuncture therapy, rabbit＇s hypothalamus was removed, and the 5-HT and NE concentrations in the hypothalamus at the peak point of the acupuncture pain threshold curve were determined by high performance liquid chromatography （HPLC）. Results： The analgesic effect was obvious at 5 min after buccal acupuncture started, peaked at 30 min, and decreased to the lowest value at 240 rain. Rabbits in the body acupuncture group began to show significant analgesic effect at 15 min, which was peaked at 30 min, and began to decline at 60 min. The pain threshold at 240 min was still higher than that at 0 mino Compared with the model group, the concentrations of hypothalamic 5-HT in the buccal acupuncture group and the body acupuncture group was significantly increased, and the between-group differences were statistically significant （both P〈0.05）. The NE/5-HT ratios in hypothalamus in the buccal acupuncture group and the body acupuncture group were significantly lower than the ratio in the model group, and the differences were statistically significant （both P〈0.05）; difference in the decrease was statistically significant between the buccal acupuncture group and the body acupuncture group （P〈0.05）. Conclusion： The analgesic effect of buccal acupuncture shows an obvious time-dependent curve. It is characterized by rapid onset of pain relief, rapid increase and decline in pain threshold. 5-HT and NE levels in rabbit＇s hypothalamus can be affected by buccal acupuncture, with increased 5-HT concentration and reduced NE/5-HT rati0.

Biparental behavior in the burying beetle Nicrophorus orbicollis： a role for dopamine？

Burying beetles Nicrophorus orbicollis exhibit facultative biparental care of young. To reproduce, a male-female burying beetle pair bury and prepare a small vertebrate carcass as food for its altricial young. During a breeding bout, male and female behavior changes synchronously at appropriate times and is coordinated to provide effective care for offspring. Although the ecologicaJ and evolutionary factors that shape this remarkable reproductive plasticity are well characterized, the neuromodulation of parental behavior is poorly understood. Juvenile hormone levels rise dramat- ically at the time beetle parents accept and feed larvae, remain highly elevated during the stages of most active care and fall abruptly when care is terminated. However, hormonal fluctuations alone cannot account for this elaborate control of reproduction. The biogenic amines octopamine （OA）, dopamine （DA）, and serotonin （5-HT） mediate a diversity of insect reproductive and social behav- iors. In this study, we measured whole brain monoamine levels in individual male and female bury- ing beetles and compared OA, DA, and 5-HT profiles between breeding （parental） and nonbreed- ing, unmated beetles. Remarkably, after 24 h of care, when parental feeding rates begin to peak, DA brain levels increase in breeding beetles when compared to nonbreeding controls. In contrast, brain OA and 5-HT levels did not change significantly. These results provide the first evidence for a potential role of DA in the modulation of burying beetle parental behavior.

Efficacy and effect on related brain-gut peptides of acupoint sticking therapy for functional dyspepsia

Objective:To observe the efficacy of acupoint sticking with Jianpi Tongjing Zhitong ointmerrt in the treatment of functional dyspepsia due to liver-qi stagnation and spleen deficiency and its effect on serum 5-hydroxytryptamine(5-HT)and ghrelin con tents.Methods:One hun dred patients with functi onal dyspepsia due to liver-qi stag nation and spleen deficiency were divided into a treatment group and a control group by the random number table method,with 50 cases in each group.The treatment group received acupoint sticking with Jianpi Tongjing Zhitong ointment and the control group was treated with mosapride citrate orally.Patients were treated for 4 weeks as a course.The therapeutic efficacy was compared after one-course treatment and the differences in gastric emptying rate,and serum 5-HT and ghrelin contents between groups were compared before and after treatment.Results:The total effective rate was 79.6%in the control group and 89.4%in the treatment group,showing significantly differe nt between groups(P<0.05).After treatme nt,the gastric empt ying rate and serum ghreli n con tent of the two groups in creased significantly,and the serum 5-HT content decreased significantly,the intra-group differe nces were significant(all P<0.01).After treatment,the gastric emptying rate and serum ghrelin content were significantly higher in the treatment group than those in the control group,while the serum 5-HT was significant lower in the treatment group,the inter-group differences were significant(all P<0.05).A negative correlation(r=-0.59)was observed between serum 5-HT content and gastric emptying rate,and a positive correlation(r=0.64)was observed between serum ghrelin content and gastric emptying rate,showing statistical significance(all P<0.01).Conclusion:Acupoint sticking with Jianpi Tongjing Zhitong ointment has a remarkable ciinical efficacy in treating patie nts with functional dyspepsia due to liver-qi stagnation and spleen deficiency and is able to in fluence the secretion of serum 5-HT and ghrelin-1 mproving the gastrointestinal motility through the regulation of related brain-gut peptides is suggested as an underlying mechanism for this therapy.

Role of brain serotonin in modulating fish behavior

The organization of the brain serotonergic system appears to have been highly conserved across the vertebrate subphylum. In fish as well as in other vertebrates, brain serotonin （5-HT）, mainly acts as a neuromodulator with complex effects on multiple functions. It is becoming increasingly clear that acute and chronic increase in brain 5-HT neurotransmission have very different effects. An acute 5-HT activation, which is seen in both winners and losers of agonistic interactions, could be related to a general arousal effect, whereas the chronic activation observed in subordinate fish is clearly linked to the behavioral inhibition displayed by these individuals. Fish displaying diver- gent stress coping styles （proactive vs. reactive） differ in 5-HT functions. In teleost fish, brain monoaminergic function is also related to life history traits.

Effect of soothing-liver and nourishing-heart acupuncture on early selective serotonin reuptake inhibitor treatment onset for depressive disorder and related indicators of neuroimmunology:a randomized controlled clinical trial

OBJECTIVE:To observe the effect of soothing-liver and nourishing-heart acupuncture on selective serotonin reuptake inhibitor(SSRIs) treatment effect onset in patients with depressive disorder and related indicators of neuroimmunology.METHODS:Overall,126 patients with depressive disorder were randomly divided into a medicine and acupuncture-medicine group using a random number table.Patients were treated for 6 consecutive weeks.The two groups were evaluated by the Montgomery-Asberg Depression Rating Scale(MADRS) and Side Effects Rating Scale(SERS) to assess the effect of the soothing-liver and nourishing-heart acupuncture method on early onset of SSRI treatment effect.Changes in serum 5-hydroxytryptamine(5-HT) and inflammatory cytokines before and after treatment were recorded and compared between the medicine group and the acupuncture-medicine group.RESULTS:The acupuncture-medicine group had significantly lower MADRS scores at weeks 1,2,4,and 6 after treatment compared with the medicine group(P < 0.01).The acupuncture group had significantly lower SERS scores at weeks 1,2,4,and 6 after treatment compared with the medicine group(P < 0.01).At 6 weeks after treatment,serum 5-HT in the acupuncture-medicine group was significantly higher compared with the medicine group(P <0.01).lnterleukin-6(IL-6) in the acupuncture-medicine group was significantly lower than that in the medicine group(P < 0.01),whereas there was no significant difference in IL-1(3 between the groups(P > 0.05).Anti-inflammatory cytokines IL-4 and IL-10 were significantly higher in the acupuncture-medicine group compared with the medicine group(P < 0.01,P < 0.05,respectively).CONCLUSION:The soothing-liver and nourishing-heart acupuncture method can effectively accelerate the onset of SSRI effects when treating depressive disorder and can significantly reduce the adverse reactions of SSRIs.Moreover,acupuncture can enhance serum 5-HT and regulate the balance of pro-inflammatory cytokines and anti-inflammatory cytokines.

Effects of electroacupuncture on the behaviors and expressions of hippocampal neurotransmitters and Bax/Bcl-2 proteins in rat models of anxiety disorder

Objective:To investigate the effects of electroacupuncture(EA)on the behaviors of rat with anxiety disorder,and the expressions of hippocampal neurotransmitters including 5-hydroxytryptamine(5-HT),norepinephrine(NE)and dopamine(DA),and the expressions of hippocampal B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X(Bax).Methods:Forty-six male Wistar rats were randomly divided into a control group(n=10);a model group(n=12),an EA group(n=12),and a drug group(n=12).Except the control group,the other three groups were established into rat models of anxiety disorder using uncertain empty bottle stimulation.Rats in the EA group and the drug group received corresponding interventions for 15 consecutive days[EA group was given EA at Baihui(GV 20)and Sanyinjiao(SP 6);the drug group was given aqueous solution of alprazolam via intragastric administration].After intervention,all four groups received open-field test(OFT)and elevated plus-maze(EPM)for behavioral evaluations.The expressions of 5-HT,NE and DA in hippocampus were determined by fluorescence spectroscopy(FS)while the expressions of Bcl-2 and Bax proteins in hippocampus were determined by Western blot(WB).Results:The OFT horizontal scores in the control group,EA group and drug group were significantly higher than that in the model group(all P<0.05),and the difference between the EA group and the drug group was statistically insignificant(P>0.05);the OFT vertical scores in the model group,EA group and drug group were significantly lower than the score in the control group(all P<0.05).The EPM percent of open-arm entries(OE%)in the control group,EA group and drug group was higher than that in the model group(P<0.05),and the differences among these three groups were statistically insignificant(P>0.05);though the percent of open-arm total time(OT%)in the EA group was lower than that in the control group(P<0.05);the difference was statistically insignificant when compared with the drug group(P>0.05),and it was significantly higher than that in the model group(P<0.05).The expression of 5-HT in the EA group was higher than that in the control group(P<0.05);the expression of 5-HT in the EA group was significantly lower than that in the model group(P<0.05);the difference between the EA group and the drug group was statistically insignificantly(P>0.05).The expression of NE in the model group was significantly higher than that in the other three groups(P<0.0S),and there was no significant difference among these three groups(P>0.05).The expression of DA in the EA group was significantly higher than that in the control group and the drug group(both P<0.05),while the difference between the EA group and the model group was statistically insignificant(P>0.05).The expression of Bax in the model group was significantly higher than that in the other three groups(all P<0.05),whereas the expression of Bcl-2 in the model group was significantly lower than that in the other three groups(all P<0.05),and the differences in both Bax and Bcl-2 among the other three groups were statistically insignificant(all P>0.05).Bax/Bcl-2 in the EA group was significantly higher than that in the control group(P<0.05)and lower than that in the model group(P<0.05),and the difference was statistically insignificant when compared with the drug group(P>0.05).Conclusion:EA shows promising effects in attenuating rats'anxiety disorder,which may be achieved by the down-regulation of the expressions of 5-HT and NE in the hippocampus and/or inhibition of hippocampal neuronal apoptosis.The efficacy is comparable to that of intervention with alprazolam.

Assessment strategies and fighting patterns in animal contests： a role for serotonin？

Accurate assessment of the probability of success in an aggressive confrontation with a conspecific is critical to the survival and fitness of the individuals. Various game theory models have examined these assessment strategies under the assumption that contests should favor the animal with the greater resource-holding potential （RHP）, body size typically being the proxy. Mutual assessment asserts that an individual can assess their own RHP relative to their opponent, allowing the inferior animal the chance to flee before incurring unnecessary costs. The model of self-determined persistence, however, assumes that an individual will fight to a set personal threshold, independ- ent of their opponent＇s RHP. Both models have been repeatedly tested using size as a proxy for RHP, with neither receiving unambiguous support. Here we present both morphological and neuro- physiological data from size-matched and mismatched stalk-eyed fly fights. We discovered differ- ing fighting strategies between winners and losers. Winners readily escalated encounters to higher intensity and physical contact and engaged in less low-intensity, posturing behaviors compared with losers. Although these fighting strategies were largely independent of size, they were associ- ated with elevated levels of 5-HT. Understanding the neurophysiological factors responsible for mediating the motivational state of opponents could help resolve the inconsistencies seen in cur- rent game theory models. Therefore, we contend that current studies using only size as a proxy for RHP may be inadequate in determining the intricacies of fighting ability and that future studies investigating assessment strategies and contest outcome should include neurophysiological data.

Effect of Transcutaneous Electrical Acupoint Stimulation on Rats with Chronic Exercise-induced Fatigue

Objective： To observe the effect of transcutaneous electrical acupoint stimulation （TEAS） on the rats with exercise-induced fatigue. Methods： Rat model of chromic exercise-induced fatigue was established with increasing load treadmill walking method. The TEAS therapy was operated immediately and 3 h after the exercise from the sixth week. Hippocampal morphology and hypothalamic morphology were observed with HE staining and the expressions of 5-hydroxytryptamine （5-HT） in hippocampus and hypothalamus were tested with immunohistochemical （IHC） staining after 2-week treatment. Results： TEAS released the damage of hippocampal morphology and hypothalamic morphology induced by exercise significantly and reduced the expression of 5-HT in hippocampus and hypothalamus. The difference between the therapy operated immediately and 3 h after exercise was not significant. Conclusion： TEAS could improve the fatigue recovery and athletic ability. The improvement of TEAS on the rats with exercise-induced fatigue was related with the decreased expression of central 5-HT and the reduction of damaged nerve cells.

Forced swimming stress does not affect monoamine levels and neurodegeneration in rats

Objective The current study was aimed to investigate the correlations between immobility time in the forced swimming test （FST, a behavioral indicator of stress level） and hippocampal monoamine levels （markers of depression）, plasma adrenalin level （a peripheral marker of stress） as well as fluoro-jade C staining （a marker of neurodegeneration）. Methods Male Sprague-Dawley rats were subjected to acute, sub-chronic （7 d） or chronic （14 d） FSTs and immobility time was recorded. Levels of noradrenalin, serotonin and dopamine in the hippocampus, and adrenalin level in the plasma were quantified by high-performance liquid chromatography with electrochemical detection. Brain sections from rats after chronic forced swimming or rotenone treatment （3 mg/kg subcutaneously for 4 d） were stained with fluoro-jade C. Results The rats subjected to swimming stress （acute, sub-chronic and chronic） showed long immobility times [（214 ± 5）, （220 ± 4） and （231 ± 7） s, respectively], indicating that the animals were under stress. However, the rats did not exhibit significant declines in hippocampal monoamine levels, and the plasma adrenalin level was not significantly increased compared to that in unstressed rats. The rats that underwent chronic swimming stress did not manifest fluoro-jade C staining in brain sections, while degenerating neurons were evident after rotenone treatment. Conclusion The immobility time in the FST does not correlate with markers of depression （monoamine levels） and internal stress （adrenalin levels and neurodegeneration）, hence this parameter may not be a true indicator of stress level.

Effects of electrical stimulation of dorsal raphe nucleus on neuronal response properties of barrel cortex layer IV neurons following long-term sensory deprivation

Objective To evaluate the effect of electrical stimulation of dorsal raphe nucleus（DRN）on response properties of layer IV barrel cortex neurons following long-term sensory deprivation.Methods Male Wistar rats were divided into sensory-deprived（SD）and control（unplucked）groups.In SD group,all vibrissae except the D2 vibrissa were plucked on postnatal day one,and kept plucked for a period of 60 d.After that,whisker regrowth was allowed for 8-10 d.The D2 principal whisker（PW） and the D1 adjacent whisker（AW）were either deflected singly or both deflected in a serial order that the AW was deflected 20 ms before PW deflection for assessing lateral inhibition,and neuronal responses were recorded from layer IV of the D2 barrel cortex.DRN was electrically stimulated at inter-stimulus intervals（ISIs）ranging from 0 to 800 ms before whisker deflection.Results PW-evoked responses increased in the SD group with DRN electrical stimulation at ISIs of 50 ms and 100 ms,whereas AW-evoked responses increased at ISI of 800 ms in both groups.Whisker plucking before DRN stimulation could enhance the responsiveness of barrel cortex neurons to PW deflection and decrease the responsiveness to AW deflection. DRN electrical stimulation significantly reduced this difference only in PW-evoked responses between groups.Besides,no DRN stimulation-related changes in response latency were observed following PW or AW deflection in either group.Moreover, condition test（CT）ratio increased in SD rats,while DRN stimulation did not affect the CT ratio in either group.There was no obvious change in 5-HT2A receptor protein density in barrel cortex between SD and control groups.Conclusion These results suggest that DRN electrical stimulation can modulate information processing in the SD barrel cortex.