Effects of Acupuncture on Monoamine Neurotransmitters in Raphe Nuclei in Obese Rats

Effects of acupuncture on the levels of neurotransmitters in the raphe nuclei were investigated in obeserats.It was found that the levels of tryptophan (Trp) and 5-hydroxyindoleacetic acid (5-HIAA) wereincreased,and 5-hydroxytryptamine (5-HT) level and 5-HT/5-HIAA ratio decreased in the raphe nucleiof the obese group as compared with the normal group;and that acupuncture could produce weightreduction,increase the 5-HT level and 5-HT/5-HIAA ratio,and decrease the contents of Trp and5-HIAA,but did not change the levels of dopamine (DA) and noradrenaline (NA).It is indicated thatbenign regulative action of acupuncture on 5-HT and its metabolism in the raphe nuclei is possibly oneof the factors for reducing weight by acupuncture.

Effects of Fuhe decoction on behaviors and monoamine neurotransmitters in different brain regions of CUMS combined with social isolation depression model rats

Objective:To investigate the effect of Fuhe decoction on the behavior and levels of monoamine neurotransmitters in different brain regions in a depression rat model induced by chronic unpredictable mild stimulation(CUMS)combined with social isolation.Methods:Fifty male SD rats were randomly divided into a blank group,model group,fluoxetine group,Chaiqinwendan decoction group,and Fuhe decoction group.Chronic unpredictable mild stimulation combined with a social isolation method was used to replicate the depression rat model.After 42 days of administration,a tail suspension test and high-performance liquid electrochemical detection(HPLC-ECD)were used to detect the behavioral changes and changes in the content of monoamine neurotransmitters norepinephrine(NE),dopamine(DA),5-hydroxytrytamine(5-HT),and metabolites in different brain regions of rats in each group before and after treatment.Results:Compared with the model group,the epinephrine(E)content in the Fuhe decoction group was highly significantly increased(P<.01).Compared with the model group,the 5-HT content of the prefrontal cortex in rats in the Fuhe decoction group was highly significantly increased(P<.01).Furthermore,compared with the model group,the 5-HT content in the hippocampus of rats in the Fuhe decoction group was significantly increased(P<.05).Conclusion:Fuhe decoction can improve the depression-like behaviors of model rats,and its antidepressant effect may be related to the increase in 5-HT content in the prefrontal cortex and hippocampus of rats.

Effects of Yulangsan polysaccharide on monoamine neurotransmitters, adenylate cyclase activity and brain-derived neurotrophic factor expression in a mouse model of depression induced by unpredictable chronic mild stress

The present study established a mouse model of depression induced by unpredictable chronic mild stress. The model mice were treated with Yulangsan polysaccharide （YLSPS; 150, 300 and 600 mg/kg） for 21 days, and compared with fluoxetine-treated and normal control groups. Enzyme-linked immunosorbent assay, radioimmunity and immunohistochemical staining showed that following treatment with YLSPS （300 and 600 mg/kg）, monoamine neurotransmitter levels, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression were significantly elevated, and depression-like behaviors were improved. Open-field and novelty-suppressed feeding tests showed that mouse activity levels were increased and feeding latency was shortened following treatment. Our results indicate that YLSPS inhibits depression by upregulating monoamine neurotransmitters, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression.

Altered serous levels of monoamine neurotransmitter metabolites in patients with refractory and non-refractory depression

The study examined plasma metabolite changes of monoamine neurotransmitters in patients with treatment-resistant depression （TRD） and non-TRD before and after therapy. All 30 TRD and 30 non-TRD patients met the diagnostic criteria for a depressive episode in accordance with the International Classification of Diseases, Tenth Revision. Before treatment, and at 4, 6, and 8 weeks after treatment, the plasma metabolite products of monoamine neurotransmitters in TRD group, including 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenyl ethylene glycol and homovanillic acid, were significantly lower than those in the non-TRD group. After two types of anti-depressive therapy with 5-serotonin and norepinephrine reuptake inhibitor, combined with psychotherapy, the Hamilton Depression Rating Scale scores were significantly reduced in both groups of patients, and the serous levels of 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenyl ethylene glycol were significantly increased. In contrast, the homovanillic acid level exhibited no significant change. The levels of plasma metabolite products of peripheral monoamine neurotransmitters in depressive patients may predict the degree of depression and the therapeutic effects of treatment.

Effects of routine rehabilitation therapy combined with low frequency electrical stimulation on monoamine neurotransmitters, NSE, ET-1 and cerebral hemodynamics in children with cerebral palsy

Objective:To investigate the effects of routine rehabilitation therapy combined with low frequency head stimulation on monoamine neurotransmitters, neuron-specific enolase (NSE), endothelin-1 (ET-1) and cerebral hemodynamics in children with cerebral palsy.Methods:From January 2017 to June 2018, 110 children with cerebral palsy were randomly divided into observation group (55 cases) and control group (55 cases). The control group received routine rehabilitation treatment, while the observation group received low-frequency head stimulation on the basis of routine rehabilitation treatment. The changes of dopamine (DA), norepinephrine (NE), serotonin (5-HT), NSE, ET-1 levels and mean blood flow velocity of anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA) were compared in two groups.Results:Before treatment, there was no significant difference in DA, NE and 5-HT levels in two groups. After treatment, DA, NE and 5-HT levels in the observation group were (192.23±22.71) ng/mL, (98.02±11.71) ng/L, (210.07±25.03) ng/L, and in the control group. the DA, NE, 5-HT levels were (147.06±17.02) ng/mL, (83.07±11.15) ng/L, and (171.88±20.45) ng/L, respectively. The DA, NE and 5-HT levels in two groups were higher than those before treatment, and DA, NE and 5-HT levels in the observation group were higher than those in the control group. Before treatment, there was no significant difference in NSE and ET-1 levels between the two groups. After treatment, the NSE and ET-1 levels in the observation group were (7.97±2.07) μg/L and (41.01±10.07) pg/mL, and the NSE and ET-1 levels in the control group were (10.38±3.02) μg/L, (58.46±15.02) pg/mL, respectively. the NSE and ET-1 in two groups were lower than those before treatment, and the NSE and ET-1 of the observation group were lower than the control group. Before treatment, there was no significant difference in mean blood flow velocity between ACA, MCA and PCA. After treatment, the mean blood flow velocities of ACA, MCA, and PCA in the observation group were (46.88±7.72) cm/s, (59.85±10.18) cm/s, and (49.15±7.02) cm/s, respectively, which was significantly higher than before treatment and higher than that of the control group in the same period.Conclusion: Conventional rehabilitation combined with low-frequency electrical stimulation of the head can effectively increase the content of monoamine neurotransmitters in children with cerebral palsy, enhance cerebral blood circulation, and reduce brain damage.

Effects of low frequency electrical stimulation on monoamine neurotransmitters,cerebral blood flow and hemorheology in children with cerebral palsy

Objective: To investigate the effects of low frequency electrical stimulation on monoamine neurotransmitters, cerebral blood flow and hemorheology in children with cerebral palsy. Methods: A total of 83 children with cerebral palsy were divided into the control group (n=42) and the observation group (n=41) according to the random data table, patients in the control group were treated with routine rehabilitation treatment, on this basis;the children in the observation group were treated with low-frequency electric stimulation. Before and after the treatment, the levels of monoamine neurotransmitter [dopamine (DA) and 5-hydroxy tryptamine (5-HT) and norepinephrine (NE)], cerebral blood flow [the average blood flow velocity of anterior cerebral artery (ACA), middle cerebral artery (MCA) and posterior cerebral artery (PCA)] and blood rheology index [high/low shear whole blood viscosity, plasma viscosity and fibrinogen (FIB)] of two groups were compared. Results: Before treatment, there were no significant difference of the levels of DA, 5-HT, NE, the average blood flow velocity of ACA/MCA/PCA, high/low shear whole blood viscosity, plasma viscosity and FIB between the two groups. After treatment, two groups of DA, 5-HT and NE levels were significantly higher than those in the same group before treatment, and the observation group of DA, 5-HT and NE levels were significantly higher than those of the control group, the difference was statistically significant;The average blood flow rate of ACA/MCA/PCA in the observation group after treatment was significantly higher than those in the same group before treatment;After treatment, the levels of high shear/low shear blood viscosity, plasma viscosity and FIB of the two groups were significantly lower than those in the same group before treatment, and the levels of observation group after treatment were significantly lower than that in the control group, the difference was statistically significant. Conclusion: Low frequency electrical stimulation can effectively increase the level of monoamine neurotransmitter, improve the level of cerebral blood flow and hemorheology, has an important clinical value.

Effect of Lirukang Oral Liquid(利乳康口服液) on Neurotransmitters and Estrogen in Rats with Hyperplasia of Mammary Gland

Objective: To investigate the effects of Lirukang oral liquid (LRK, 利乳康口服液) on release of neurotransmitter in rats with hyperplasia of mammary glands (HMG) and to explore its mechanism. Methods: Sixty rats were divided into six groups, the normal control group, the model control group, the large dosage (3.6g/kg) and the small dosage (1.8g/kg ) LRK groups, the Ruzengning (乳增宁, RZN, 2.5g/kg) group and the tamoxifen (TAM, 5mg/kg) group, 10 in each group. Except those in the normal control group, all the animals were made into rat model of HMG by intraperitoneal injection of estradiol benzoate. Levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) in hypothalamus and mammary gland in rats were detected by fluorescence luminosity assay, and level of prolactin (PRL) in serum was detected by radioimmunoassay. Results: In the model group, the level of DA reduced significantly ( P<0. 01), and 5-HT and PRL increased obviously ( P<0.01). Compared with the model group, the LRK groups of both dosages and the TAM group had their level of DA significantly increased (P<0. 01), and level of 5-HT significantly decreased ( P<0.01). The serum PRL in both LRK groups was significantly decreased ( P<0. 01). No obvious changes in DA, 5-HT and PRL were found in the RZN group. Conclusion: LRK and TAM have similar effects in regulating the release of neurotransmitter in hypothalamus and mammary gland and serum content of estrogen in the animal models of HMG.

Effects of Mulberry Extract on Regulation of Sex Hormone and Hypothalamic Neurotransmitter in Naturally Aged Female Rats

[Objective] This study aimed to investigate the effects of different mulberry extracts on sex hormone and hypothalamic neurotransmitter in naturally aged female rats and reveal the mechanism and material basis of anti-aging effect of mulberry. [ Method] Fourteen-month-old SD female rats were selected and ran- domly divided into model group, positive control group, high-dose and low-dose water extract groups, high-dose and low-dose 50% ethanol extract groups, and high-dose and low-dose 95% ethanol extract groups; four-month-old SD female rats were used as blank control group. After eight weeks of drug administration, the levels of 17β-estradiol （E2 ）, follicle- stimulating hormone （FSH） and luteinizing hormone （LH） in serum and beta-endorphin （β-EP） in hypothalamus were de- termined by radioimmunoassay; the levels of norepinephrine （ NE）, dopamine （ DA）, 5-hydroxy tryptamine （5-HT） and 5-HIAA in hypothalamus were determined by fluorescence spectrometry. [ Result] Water extract of mulberry can increase the level of E2 and reduce levels of FSH and LH in serum, and increase the level of fl-EP and reduce levels of DA, 5-HT and 5-HIAA in hypothalamus of naturally aged female rats. Water extract of mulberry exhibited higher effects than 50% eth- anol extract and 95% ethanol extract. [ Conclusion] Mulberry could significantly improve the function of hypothalamic peptide neurotransmitter in naturally aged rats, correct disorders of hypothalamic monoamine neurotransmitter, and treat perimenopausal syndrome by regulating reproductive endocrine function, which might be related with its water-soluble components and require further investigation and development.

Xylene-induced Effects on Brain Neurotransmitters, Behavior and Fos Protein in Rats

Male Sprague-Dawley rats administered xylene intrapetitoneally on alternate days at a dose of 125 or 250mg/kg for 30 days exhibited no marked changes in locomotor activity, learning and memory capacity. However in rats given xylene on alternate day at a dose of 500 mg/kg for 30 days, a significant decrease in locomotor activity, deficits in leaming ability and memory loss were detected. These xylene-induced behavioral ehanges were assoryiated with a decrease in fyendorphin and leuenkaphlin concentrations in the pons-medulla. On the contrary, xylene at a dose of 500mg/kg increased the β-endorphin level in caudate and c-fos expression in hippocampus. These data suggest that the xylene-induced behavioral alterations might be associated with the expression of Fos protein in the hippocampus.

Effects of Schisandra B on neurotransmitter contents, inflammation and oxidative stress in hippocampus of depression model rats

Objective:To study the effects of Schisandra B on neurotransmitter content,inflammation and oxidative stress in the hippocampus of depression model rats.Methods:A total of 30 male SD rats were randomly divided into the control group,the model group,and the Schisandra B group.The latter two groups established depression model according to chronic mild unpredictable stress.The Schisandrin B group was given Schisandrin B gavage for 6 weeks.The differences in depressive behavior and hippocampal neurotransmitter,inflammatory index,oxidative stress index were compared among the three groups.Results:Compared with the control group,the sugar preference score was significantly lower;the immobility time was significantly prolonged;the contents of 5-hydroxytryptamine(5-HT),norepinephrine(NE),dopamine(DA),superoxide dismutase(SOD),glutathione peroxidase(GPx)in hippocampus were significantly decreased;the contents of malondialdehyde(MDA),the expression of nuclear factor-kappa B(NF-κB),interleukin-1beta(IL-1β)and tumor necrosis factor-α(TNF-α)in hippocampus were significantly increased in the model group(P<0.05).Compared with the model group,the sugar preference score was significantly increased;immobility time significantly shortened;the contents of 5-HT,NE,DA,SOD and GPx in hippocampus were significantly increased;the content of MDA and the expression of NF-κB,IL-1βand TNF-αin hippocampus were significantly decreased in ketamine group(P<0.05).Conclusion:Low dose of Schisandra B can improve depressive behavior,increase monoamine neurotransmitter secretion,and inhibit inflammation and oxidative stress in depression model rats.

Correlation between changes of central neurotransmitter expression and stress response in mice A restraint time-course analysis

BACKGROUND： Changes in central neurotransmitter expression play an important role in stress response and forms the basis for stress-induced psychological and behavior changes. OBJECTIVE： To observe the effects of different restraint stress intervals on brain monoamine neurotransmitter expression, and to investigate the correlation between stress response and neurotransmitter levels. DESIGN： Randomized controlled animal study. SETTING： Chinese Herb and Natural Medicine Institute, Pharmacological College of Jinan University. MATERIALS： Sixty 7-week-old male Kunming mice of clean grade, weighing 18-22 g, were provided by the Guangdong Medical Experimental Animal Center. The experiment was in accordance with animal ethics standards. METHODS： This study was performed at the Chinese Herb and Natural Medicine Institute, Pharmacological College of Jinan University from June 2006 to May 2007. A restraint device for mice was constructed according to published reports. Experimental mice were adaptively fed for 1 week and randomly divided into a control group （n = 10） and an experimental group （n = 50）. The experimental group was sub-divided into five restraint intervals： 4, 8, 12, 18, and 24 hours （n = 10 mice per time point）. Animals in the experimental group were not allowed to eat or drink during the restraint period. Mice in the control group did not undergo restraint, but had identical food and water restrictions. Cerebral cortex and hypothalamus were separated based on observational times and protein was extracted using perchloric acid. Central monoamine neurotransmitter levels were measured using high performance liquid chromatography with electrochemical detection. MAIN OUTCOME MEASURES： Levels of norepinephrine （NE）, dopamine hydrochloride （DA）, 3,4-dihydroxyphen-ylanetic acid （DOPAC）, homovanillic acid （HVA）, 5-hydroxytryptamine （5-HT）, and 5-hydroxyindoleac-etic acid （5-HIAA） in the cerebral cortex and hypothalamus of mice. RESULTS： Sixty mice were included in the final analysis. ① NE levels in the cerebral cortex, hypothalamus, and plasma： four hours after restraint, NE levels in the cerebral cortex and hypothalamus ere significantly lower than control levels （P 〈 0.05）. After 12 hours of restraint, NE levels in the experimental group were significantly higher than in the control group （P 〈 0.05）. At 18 hours of restraint, there was no significant difference in NE levels in the cerebral cortex between the experimental group and the control group （P 〉 0.05）. In addition, NE levels in the plasma gradually increased with longer restraint time, which was significant between experimental groups and the control group （P 〈 0.05-0.01）. ② Levels of DA, DOPAC, and HVA in the cerebral cortex and hypothalamus： there were significant differences in DA levels in the cerebral cortex and hypothalamus after 18 and 24 hours of restraint compared to control animals （P 〈 0.05）. DOPAC and HVA levels in the cerebral cortex were enhanced with longer restraint time, and there was significant difference in all restraint groups compared to control levels （P 〈 0.01）, except for DOPAC levels after 4 hours of restraint. Moreover, DOPAC and HVA levels in the hypothalamus were enhanced with increasing restraint time. Levels of 5-HT and 5-HIAA in the cerebral cortex and hypothalamus： after short restraint periods and in the control group, 5-HT was not detectable. However, it was quantitatively detected at 12 hours after restraint. The 5-HT levels in the cerebral cortex and hypothalamus reached peak levels at 12 and 18 hours of restraint. 5-HIAA levels in the cerebral cortex and hypothalamus showed a similar tendency to increase with restraint time- 5-HIAA levels at 4-8 hours after restraint were significantly higher than control levels （P 〈 0.01）. The 5-HIAA levels decreased at 12 hours after restraint, but remained significantly higher than the control group （P 〈 0.05）. CONCLUSION： Restraint stress affects the hypothalamic-pituitary-adrenal （HPA） axis and causes changes in monoamine neurotransmitters in brain tissues, which suggests stress status could be improved by adjusting HPA axis and neurotransmitter levels in the brain.

A high-performance liquid chromatography with fluorescence detection method for the simultaneous quantitation of monoamine neurotransmitters and their metabolites in subregions of rat brain

Abstract： In the presem study, we simultaneously quantified the levels of monoamine neurotransmitters （MANTs） and their metabolites （levodopa, norepinephrine, epinephrine, dopamine, 5-HT, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindole-3-acetic acid） in different brain subregions of rats using a newly developed simple, sensitive and selective high-performance liquid chromatography with fluorescence detection （HPLC-FLD） method. In this new HPLC-FLD method, analytes were directly extracted and separated without deriveatization step within 20 min. The FLD wavelength was set at 280 nm and 330 nm for excitation and emission, respectively. The analytes were separated on an Agilent Eclipse Plus Cls column （4.6 mm×150 mm, 5.0 μm） equipped with an Agilent XDB-C18 security guard column （4.6 mm×12.5 mm, 5.0 lam）, and the column temperature was maintained at 35 ℃. The mobile phase for elution was isocratic. The mobile phase consisted of citric acid buffer （50 mmol/L citric acid, 50 mmol/L sodium acetate, 0.5 mmol/L octane sulfonic acid sodium salt, 0.5 mmol/L Na2EDTA and 5 mmol/L triethylamine, pH 3.8） and methanol （90：10, v/v） at a flow rate of 1.0 mL/min. The detection limit （DL） was 0.9-23 nM for all the MANTs and their metabolites with a sample volume of 50 μL. The method was shown to be highly reproducible in terms of peak area （intraday, 0.08%-1.85% RSD, n = 5）. The simultaneous measurement of these MANTs and their metabolites improved our understanding of the neurochemistry in the central nervous system （CNS） in relation to different addictive drugs （methamphetamine, heroin and their mixture） in drug-addicted rat models.

Effect of anxiety and depression on serum neurotransmitters and immune function in patients with cervical cancer chemotherapy

Objective:To study the effect of anxiety and depression on serum neurotransmitters and immune function in patients with cervical cancer chemotherapy.Methods:Patients with advanced cervical cancer who received chemotherapy in the First Affiliated Hospital of Chengdu Medical College between May 2014 and June 2016 were selected, HAMA scores and HAMD scores were used to assess anxiety and depression and divide the patients into control group, depression group, anxiety group and depression + anxiety group. The contents of monoamine neurotransmitters and immune cytokines in serum as well as the expression of immune transcription factors in peripheral blood mononuclear cells were detected.Results:Serum NE, E, 5-HT, 5-HIAA and DOPAC contents of depression group and depression + anxiety group were significantly lower than those of control group, and serum NE, E, 5-HT, 5-HIAA and DOPAC contents of anxiety group were significantly higher than those of control group;peripheral blood T-bet mRNA expression as well as serum IFN-γ and TNF-α contents of depression group, anxiety group and depression + anxiety group were significantly lower than those of control group while GATA3, Foxp3 and RORγt mRNA expression as well as serum IL-4, TGF-β and IL-17 contents were significantly higher than those of control group;peripheral blood T-bet mRNA expression as well as serum IFN-γ and TNF-α contents of depression + anxiety group were significantly lower than those of depression group and anxiety group while GATA3, Foxp3 and RORγt mRNA expression as well as serum IL-4, TGF-β and IL-17 contents were significantly higher than those of depression group and anxiety group. Conclusion: Anxiety and depression in patients with cervical cancer chemotherapy can affect the secretion of monoamine neurotransmitters, the differentiation of CD4+T cell subsets and the antitumor immune response mediated by them.

The bio-active components of the Mongolian medicine Horcha-6 and therapeutic mechanism in the rat migraine model

Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treating migraines through the use of network pharmacology and a rat migraine model.Methods:After identifying the active components of Horcha-6,the corresponding genes of the active components’target were obtained from the Universal Protein database,and a“compound-target-disease”network was constructed using Cytoscape 3.9.0 software.For the in vivo experiments,nitroglycerin was injected intraperitoneally into rats to create a migraine model.Pre-treatment with Horcha-6 was administered orally for 14 days,and rats were subjected to migraine-related behavior tests.RNA sequencing was performed to identify the gene expression regulated by Horcha-6 in the trigeminal nerve.Results:A total of 903 chemical components of Horcha-6 have been collected in the liquid chromatography with tandem mass spectrometry.We discovered 55 of the Horcha-6 bio-active components that were evaluated based on their Percent Human Oral Absorption(≥30%)and DL values(≥0.185)on the traditional Chinese medicine systems pharmacology database.The“compound-target-disease”network contained 163 intersection targets with the migraine state.Gene Ontology analysis indicated that these components significantly regulated the immune response,vascular function,oxidative stress,etc.When Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed,we observed that most of the target genes were significantly enriched in the inflammation and neuro-related signaling pathway,toll-like receptor signaling pathway,neuroactive ligand-receptor interaction,etc.These predictions were further demonstrated via in vivo animal model experiments.The RNA sequencing results showed that 41 genes were down-regulated(P<0.05)and 86 genes were up-regulated(P<0.05)in the Horcha-6 treated group compared with the untreated group.Those genes were mainly involved in neuromodulation,vascular function,and hormone metabolism.Conclusion:The 55 bio-active components in Horcha-6 regulate inflammation,hormone metabolism,and neurotransmitters and have potential as a therapy to treat migraines.

Effects of Kaixin Jieyu Decoction(开心解郁汤)on Behavior, Monoamine Neurotransmitter Levels, and Serotonin Receptor Subtype Expression in the Brain of A Rat Depression Model

Objective： To determine the mechanisms underlying the anti-depressant effects of Kaixin JieyuDecoction （开心解郁汤, KJD） by investigating the effects of KJD on behavior, monoamine neurotransmitterlevels, and serotonin （5-HT） receptor subtype expression in the brain in a rat model of depression. Methods：The rat depression model was established using chronic unpredictable mild stress （CUMS）. Forty-eight SpragueDawley rats were randomly divided into control, depression model （CUMS）, CUMS＋KJD （7.7 g/kgl-d1 ofcrude drug）, and CUMS＋fluoxetine （2.4 mg/kgl.d1） groups （n=12 in each group）, and the treatments lastedfor 21 days. We regularly evaluated body weight, sucrose consumption, and horizontal and vertical activityscores in open-field tests. The content of the monoamine neurotransmitters 5-HT, norepinephrine （NE）, anddopamine （DA） and the DA metabolite homovanillic acid in the cerebral cortex, and 5-HT1A and 5-HT2A receptormRNA in the cerebral cortex and the hippocampus, were determined respectively by high-performance liquidchromatography-coularray electrochemical detector and real-time polymerase chain reaction. Results： Comparedwith the control group, CUMS rats showed a variety of depression-like behavioral changes, including a significantreduction in body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests（P〈0.05 or ,P〈0.01）, and a significant decrease in 5-HT and NE levels and 5-HT2A receptor mRNA expression.In contrast, they showed a significant increase in 5-HT1A receptor mRNA expression in the cerebral cortex. Inthe hippocampus, 5-HT1A receptor mRNA expression was lower whereas 5-HT2A receptor mRNA expressionwas higher than in the control group （P〈0.05 or P〈0.01）. Treatment with KJD or fluoxetine partially attenuatedthese changes （,P〈0.05 or ,P〈0.01）. Conclusion： KJD could normalize the levels of 5-HT and NE and adjust thebalance of 5-HT2A and 5-HT2A receptor expression in rat cerebrum, and this may be one of mechanisms ofantidepressant effects of KJD.

Effect of Zuogui Pill(左归丸) on Monoamine Neurotransmitters and Sex Hormones in Climacteric Rats with Panic Attack

Objective： To explore the effects of Chinese medicine prescription Zuogui Pill（左归丸, ZGP） on monoamine neurotransmitters and sex hormones in climacteric rats with induced panic attacks. Methods： Forty-eight climacteric female rats were randomized into 6 groups with 8 rats in each group： the control group, the model group, the low-, medium- and high-dose ZGP groups and the alprazolam group. Rats in the low-, medium- and high-dose ZGP groups were administered 4.725, 9.45, or 18.9 g/kg ZGP by gastric perfusion, respectively. The alprazolam group was treated by gastric perfusion with 0.036 mg/kg alprazolam. The control and model groups were treated with distilled water. The animals were pretreated once daily for 8 consecutive weeks. The behaviors of rats in the open field test and the elevated T-maze（ETM） were observed after induced panic attack, and the levels of brain monoamine neurotransmitters and the plasma levels of sex hormones were measured. Results： Compared with the control group, the mean ETM escape time and the levels of 5-hydroxytryptamine（5-HT） and noradrenalin（NE） of the model group were significantly reduced（P〈0.05）, Compared with the model group, the mean ETM escape time and the 5-HT and NE levels of all the ZGP groups increased significantly（P〈0.05 or P〈0.01）. However, no significant difference was observed in the levels of sex hormones between the groups. Conclusion： Pretreatment with ZGP in climacteric rats may improve the behavior of panic attack, which may be related to increased 5-HT and NE in the brain.

Evaluation on monoamine neurotransmitters changes in depression rats given with sertraline, meloxicam or/and caffeic acid

Inflammation drives the development of depression and may affect neurotransmitters and thus neurocircuits increase the risk of depression.To investigate the influence of inhibition of inflammatory pathways on the biogenic amine neurotransmitters metabolism in depressive rats,sertraline,and meloxicam,the inhibitors of arachidonic acid-cyclooxygenase-2/lipoxygenase(AA-COX-2/5-LO)pathways,were given to depressive rats.After the development of depression model by chronic unpredictable mild stress(CUMS)for 6 weeks,Successful modeling rats were selected and randomly divided into CUMS group and medication administration group.After given medicine,The biogenic amine neurotransmitters in rat cortex and hippocampus were measured by high-performance liquid chromatography equipped with an electrochemical detector(HPLC-ECD).Compared with the normal group,the concentration of norepinephrine(NE)significantly decreased and the concentrations of Tyrosine(Tyr),Tryptophan(Trp),3,4-dihydroxyphenyl acetic acid(DOPAC),3-methoxy-4-hydroxyphenylglycol(MHPG),homovanillic acid(HVA)and 5-hydroxyindoleacetic acid(5-HIAA)significantly increased in the CUMS group.Sertraline significantly inhibited the elevation of 5-HIAA.Meloxicam inhibited the decrease of NE level in CUMS-induced rat and the increase of Trp,MHPG,and 5-HIAA level in a dose-dependent manner.Caffeic acid inhibited the decrease of NE and the increase of Trp and MHPG in a dose-dependent manner.The inhibition of AA-COX-2/5-LO pathways can improve the behaviors of depression rats and suppress CUMSinduced changes in biogenic amines.Compared with the single-dose lipoxygenase(5-LO)or Cyclooxygenase-2(COX-2)inhibitor,the combination treatment with meloxicam 1 mg/kg and caffeic acid 10 mg/kg have no significant improvement in CUMS-induced depression behavior and the level of cortical monoamine neurotransmitters and their metabolites.

Liquid chromatography-electrochemical detection for studying the effects of tetrahydrobiopterin on monoamine neurotransmitters in rat striatum

Tetrahydrobiopterin(BH4)is an essential co-factor in the biosynthesis of monoamine neurotransmitters.A nano-Pt/Pd modified electrode as the electrochemical detector(ED)for high-performance liquid chromatography(HPLC)coupled with microdialysis sampling,is used to explore the effect of administration of BH4 on the monoamine neurotransmitters in the rat striatum.The researches demonstrate that the contents of dopamine(DA),5-hydroxytryptamine(5-HT),5-hydroxyindoleacetic acid(5-HIAA)and homovanillic acid(HVA)increase significantly with the administration of BH4.The pharmaceutical kinetics is carried out to research into the time course of BH_(4) effect on the concentration of monoamine neurotransmitters in rat striatum,which pro-vides reliable data for pathology and pharmacology research on neuroscience.

Bone marrow-derived mesenchymal stem cells ameliorate sodium nitrite-induced hypoxic brain injury in a rat model

Sodium nitrite（Na NO2） is an inorganic salt used broadly in chemical industry. Na NO2 is highly reactive with hemoglobin causing hypoxia. Mesenchymal stem cells（MSCs） are capable of differentiating into a variety of tissue specific cells and MSC therapy is a potential method for improving brain functions. This work aims to investigate the possible therapeutic role of bone marrow-derived MSCs against Na NO2 induced hypoxic brain injury. Rats were divided into control group（treated for 3 or 6 weeks）, hypoxic（HP） group（subcutaneous injection of 35 mg/kg Na NO2 for 3 weeks to induce hypoxic brain injury）, HP recovery groups N-2 w R and N-3 w R（treated with the same dose of Na NO2 for 2 and 3 weeks respectively, followed by 4-week or 3-week self-recovery respectively）, and MSCs treated groups N-2 w SC and N-3 w SC（treated with the same dose of Na NO2 for 2 and 3 weeks respectively, followed by one injection of 2 × 106 MSCs via the tail vein in combination with 4 week self-recovery or intravenous injection of Na NO2 for 1 week in combination with 3 week self-recovery）. The levels of neurotransmitters（norepinephrine, dopamine, serotonin）, energy substances（adenosine monophosphate, adenosine diphosphate, adenosine triphosphate）, and oxidative stress markers（malondialdehyde, nitric oxide, 8-hydroxy-2′-deoxyguanosine, glutathione reduced form, and oxidized glutathione） in the frontal cortex and midbrain were measured using high performance liquid chromatography. At the same time, hematoxylin-eosin staining was performed to observe the pathological change of the injured brain tissue. Compared with HP group, pathological change of brain tissue was milder, the levels of malondialdehyde, nitric oxide, oxidized glutathione, 8-hydroxy-2′-deoxyguanosine, norepinephrine, serotonin, glutathione reduced form, and adenosine triphosphate in the frontal cortex and midbrain were significantly decreased, and glutathione reduced form/oxidized glutathione and adenosine monophosphate/adenosine triphosphate ratio were significantly increased in the MSCs treated groups. These findings suggest that bone marrow-derived MSCs exhibit neuroprotective effects against Na NO2-induced hypoxic brain injury through exerting anti-oxidative effects and providing energy to the brain.

EFFECTS OF MORPHINE AND MONOAMINE NEUROTRANSMITTERS ON PAIN MODULATION OF SUBSTANCE P IN THE SPINAL CORD

Substance P (SP)in the spinal cord is unevenly distributed and is concentrated in the dorsal horn, particularly in terminals of unmyelinated nociceptive primary afferent fibers. It indicates that SP may be an excitatory neurotransmitter released from nociceptive primary afferent nerve terminals. It was reported that SP in the spinal cord took part both in