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OBJECTIVE@#To reveal the effect and mechanism of Jiaotai Pill (, JTP) on insomniac rats.@*METHODS@#The insomniac model was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). In behavioral experiments, rats were divided into control, insomniac model, JTP [3.3 g/(kg•d)], and diazepam [4 mg/(kg•d)] groups. The treatment effect of JTP was evaluated by weight measurement (increasement of body weight), open field test (number of crossings) and forced swimming test (immobility time). A high performance liquid chromatography-electrochemical detection (HPLC-ECD) method was built to determine the concentration of monoamine transmitters in hypothalamus and peripheral organs from normal, model, JTP, citalopram [30 mg/(kg•d)], maprotiline [40 mg/(kg•d)] and bupropion [40 mg/(kg•d)] groups. Expressions of serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET) were analyzed by quantitative polymerase chain reaction (qPCR) and Western blot in normal, model and JTP groups. A high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) method was established to determine the pharmacokinetics, urine cumulative excretion of metformin in vivo, and tissue slice uptake in vitro, which were applied to assess the activity of organic cation transporters (OCTs) in hypothalamus and peripheral organs.@*RESULTS@#Compared with the insomniac model group, the body weight and spontaneous locomotor were increased, and the immobility time was decreased after treatment with JTP (P<0.01). Both serotonin and dopamine contents in hypothalamus and peripheral organs were increased (P<0.01). The norepinephrine content was increased in peripheral organs and decreased in hypothalamus (P<0.05 or P<0.01). At the same time, SERT, DAT, OCT1, OCT2, and OCT3 were down-regulated in hypothalamus and peripheral organs (P<0.05). NET was down-regulated in peripheral organs and up-regulated in hypothalamus (P<0.05 or P<0.01). Moreover, the activity of OCTs in hypothalamus and peripheral organs was inhibited (P<0.05).@*CONCLUSION@#JTP alleviates insomnia through regulation of monoaminergic system and OCTs in hypothalamus and peripheral organs.
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Objective: To investigate the antidepressant roles of estrogen in the perimenopausal depression rat model and po- tential mechnisms. Methods: The perimenopausal depression rat model was performed by ovariectomized(OVX)rat following unpre- dictable chronic mild stress(UCMS). The rats were divided into 6 groups:the control group(CON),OVX group,model (OVX+UC- MS)group,estrogen(estradiol,E2)treatment group,escitalopram group(ESC),and OVX+E2 group. Open filed and sucrose prefer- ence tests were used to investigate depression-like behavior. Nissl staining was used to analyze neuron numbers in the dentate gyrus (DG)region of rat hippocampus,Levels of 5-HT,5-H1AA, norepinephrine(NE)and dopamine(DA)in the hippocampus were deter- mined by the HPLC method,while the levels of several markers associated with HPA axis were determined by ELISA. Results: OVX+ UCMS decreased the number of crosses and rearings in open field test and decreased sucrose preference in sucrose preference test in the perimenopausal depression rat model. E2 treatment could reverse the depression behavior. E2 treatment also reversed the de- creased neuron numbers of DG region in the rat hippocampus and decreased monamine transmitter and high hypothalamic-pituitary-ad- renal axis(HPA)activation. Conclusion: E2 plays antidepressant roles in perimenopausal depression rat model through protecting neuron,increasing monamine transmitter level and decreasing HPA axis activation.
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Depression has become a serious global public health concern and a prominent social problem.Moreover,the majority of first-line antidepressants that target monoamine neurotransmitter function have significant limitations (ie,low response rates,a time-lag of weeks for a response,cognitive impairment and sexual dysfunction),particularly with the delayed onset of clinical effects which will reduce the patients' clinical compliance and increase the patients' risk of suicide and self-harm.All this highlights a major unmet need for a new generation of antidepressants with fast onset action and low toxic side effects.There has been great progress in the study on pathogenesis of depression and drug targets so far.Recent research has shifted from increasing the level of monoamine neurotransmitter (NE/5-HT) to focusing on regulating the adaptive and plastic change of the nervous system,especially the discovery of new potential fast-onset non-monoaminergic targets including NMDA receptor,AMPA receptor and M choline receptor.This article reviews the investigation into generalized fast antidepressants and their potential targets,in the hope of providing critical information for the development of fastonset antidepressants.
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The etiology of depression is complex, and its incidence is related to many factors, such as social factors, genetic factors, endocrine and central nervous system functions. Antidepressant treatment effect by affecting one or more factors of the depression regulation system. This paper, based on the various hypotheses on the pathogenesis of depression proposes that the depression pathogenesis may involve central monoamine neurotransmitter systems, neural nutrients, neuro-endocrine system, nervous system and the immune system, and central nervous system tissue morphology changes, and summarizes the antidepressant drug research progress.
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The etiology of depression is complex, and its incidence is related to many factors, such as social factors, genetic factors, endocrine and central nervous system functions. Antidepressant treatment effect by affecting one or more factors of the depression regulation system. This paper, based on the various hypotheses on the pathogenesis of depression proposes that the depression pathogenesis may involve central monoamine neurotransmitter systems, neural nutrients, neuro-endocrine system, nervous system and the immune system, and central nervous system tissue morphology changes, and summarizes the antidepressant drug research progress.
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@#Objective To explore the relationship between the level of synaptic monoamine transmitters and epilepsy and its severity.Methods The models of seizure were made with intraperiloneal injection. The concentrations of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in palium(Pal), hippocampus (Hip) and corpus and striatum (Str) were determined with flurospectrophotometry. Results The severity of epilepsy was negatively correlated with the level of 5-HT in all three regions (P<0.05) with that of NE in Hip (P<0.01). The level of 5-HT of three seizure groups dropped significantly, the level of DA dropped significantly only in Str (P<0.01), and the level of NE dropped significantly only in Hip (P<0.01). Conclusion Monoamine transmitters in different regions closely affect the severity and sensitivity of epilepsy depends on the level of special transmitters in different brain regions.
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Objective To explore the possible effects of nutritional supplements on brain function as reflected by Water Maze test performance in mice after +Gz exposure.Method Mice were arranged into control group (group A),+Gz group without nutritional supplementation (group B) and +Gz plus nutritional supplementation group (group C).Each group contains 12 mice.Mice in group A were not exposed to +Gz while mice in both group B and group C were exposed to 8 min +10 Gz.Distilled water was gavaged to group B mice 3 h before +Gz exposure.On the day before +Gz exposure pyridoxol fortified water was given and 3 h before exposure mixed amino acids solution were gavaged to group C mice.Water Maze test was done and scores were recorded in all groups.After the Water Maze test was completed,blood was collected through the eyes for serum amino acid determinations and brain tissue was collected by decollation for monoamine determination and γ-glutamyl transferase (GGT) activity evaluation. Result After +Gz exposure,longer completion time and more mistakes were observed in Water Maze test in group B as compared with group A and a trend of improvement in group C was noticed. The ratio of brain 5-HT to dopamine(DA) was significantly reduced in group C as compared with group B.Gamma glutamyl transferase (GGT) activity in brain tissue in group C and group B increased significantly. Conclusion High sustained +Gz exposure significantly reduces Water Maze test performance in mice (longer completion time and more mistakes).It seems that there is a trend of improvement in Water Maze performance in mice in dietary nutritional supplementation group,which might be due to significant reduction in ratio of brain 5-HT to DA in mice with nutritional supplementation.
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A rapid and simple chromatographic procedure using HPLC-ECD is described for simultaneousdetermination of NE. E. DA. 5-HT with their precursor amino acid (Tyr. Trp) and their main metabolites (HVA. 5-HIAA). Using this assay,eight substrates are measured in cortex, diencephalon and brain stem of mice duing immunological response challenged by SRB6 3 days after challenged, the DA HVA in cortex, NE in diencephalon decrease obviously (p