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With the increasing prevalence of myopia among adolescents, the pathogenesis of this condition has garnered significant attention. Studies have discovered the expression of various hormone receptors in ocular tissues of both animals and humans. Additionally, changes in hormone levels accompany the development of myopia, although the exact relationships remain inconclusive. This article reviews the potential influences and mechanisms of action of endogenous hormones such as melatonin, serotonin, insulin, glucagon, sex hormones, vitamin D, and prostaglandins in ocular tissues including the retina, choroid, and sclera. It elaborates on the relationship between fluctuations in these hormone levels and the progression of myopia, aiming to provide guidance for exploring targets for myopia prevention and control.

To investigate the antidepressant mechanism of Shenling Kaixin Granules(SLKX) in treating chronic unpredictable mild stress(CUMS) model rats. Ninety male SD rats were randomly divided into control group, model group, Shugan Jieyu Capsules(110 mg·kg~(-1)) group and SLKX low-(90 mg·kg~(-1)), medium-(180 mg·kg~(-1)), and high-dose(360 mg·kg~(-1)) groups. Depression rat model was replicated by CUMS method. After treatment, the behavioral changes of rats were evaluated by sugar preference, open field, elevated cross maze and forced swimming experiments. The contents of interleukin 1 beta(IL-1β), tumor necrosis factor α(TNF-α), brain-derived neurotrophic factor(BDNF) and 5-hydroxytryptamine(5-HT) in serum were determined by enzyme linked immunosorbent assay(ELISA), and the activities of superoxide dismutase(SOD) and catalase(CAT) in hippocampal CA1 region were also detected. Pathological changes in hippocampal CA1 region were detected by hematoxylin-eosin(HE) staining, and Western blot was used to determine the expression of nerve growth factor(NGF), BDNF, phospho-tyrosine kinase receptor(p-TrkB)/TrkB, phospho-cAMP-response element binding protein(p-CREB)/CREB, nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax) and caspase-3 in hippocampal CA1 region. RESULTS:: showed that compared with the control group, the model group had decreased sugar preference, reduced number of entries and time spent in the center of open field and shortened total distance of movement, reduced number of entries and proportion of time spent in open arm, and increased number and time of immobility in forced swimming experiment. Additionally, the serum contents of IL-1β and TNF-α and the expression of caspase-3 were higher, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1 and Bcl-2/Bax, and the Nrf2 nuclear translocation were lower in model group than in control group. Compared with the conditions in model group, the sugar preference, the number of entries and time spent in the center of open, total distance of movement, and the number of entries and proportion of time spent in open arm in treatment groups were increased while the number and time of immobility in forced swimming experiment were decreased; the serum contents of IL-1β and TNF-α and the expression of caspase-3 were down regulated, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1, Bcl-2/Bax, and Nrf2 nuclear translocation were enhanced. In conclusion, SLKX might regulate the Nrf2 nucleus translocation by activating BDNF/TrkB/CREB pathway, lower oxidative stress damage in hippocampus, inhibit caspase-3 activity, and reduce apoptosis of hippocampal nerve cells, thereby playing an antidepressant role.

Objective: To investigate the effect of midazolam on pain in lumbar disc herniation model rats based on p38 MAPK signaling pathway., Methods: Fifty SPF-grade Sprague-Dawley healthy rats, half male and half female, were selected and randomly divided into normal group, model group, and low-dose, medium-dose, high-dose groups. Model group and low-dose, medium-dose, high-dose groups were initially modeled for lumbar disc herniation. Intraperitoneal injection of saline was performed in rats of normal and model groups; and in the low-dose, medium-dose, and high-dose groups, intraperitoneal injection of midazolam was performed with doses of 30, 60, and 90 mg/kg, respectively. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), β-endorphin (β-EP), substance P (SP), neuropeptide Y (NPY) were detected in the serum of rats by enzyme-linked immunoassay. The expression of p38 MAPK and matrix metalloproteinase-3(MMP-3) protein were detected by Western blot in the tissues of rats of each group., Results: The levels of TNF-α, IL-1β and β-EP were higher and the level of 5-HT was lower in the model group than in the normal group( P <0.05);the levels of TNF-α, IL-1β and β-EP were lower and the level of 5-HT was higher in the low-dose, medium-dose and high-dose groups than in the model group( P <0.05). The levels of SP and NPY increased in the model group compared with the normal group ( P <0.05) and the levels of SP and NPY decreased in the low-dose, medium-dose and high-dose groups compared with the model group ( P <0.05). The expression of p38 MAPK and MMP-3 increased in the model group compared with the normal group ( P <0.05); the expression of p38 MAPK and MMP-3 decreased in the low-dose, medium-dose and high-dose compared with the model group( P <0.05)., Conclusion: Midazolam may ameliorate the immune inflammatory response in rats with a model of lumbar disc herniation, possibly regulated through the p38MAPK signaling pathway.

Objective: To observe the effect of electroacupuncture (EA) at "Zhongliao" (BL33) and "Xialiao" (BL34) on the 5-hydroxytryptamine (5-HT) signaling system in colon tissue and short-chain fatty acids in feces of rats with slow transit constipation (STC), so as to explore the underlying mechanisms of EA in the treatment of STC., Methods: A total of 32 SD rats were randomly divided into normal, model, drug control and EA groups, with 8 rats in each group. The STC model was established by intragastric administration of loperamide for 14 days. The EA stimulation (2 Hz/15 Hz) was performed at bilateral BL33 and BL34 for 30 min, once a day for 14 days. The first black stool de-fecation time and fecal water content were detected after treatment. The expressions of 5-hydroxytryptamine 4 receptor (5-HT4R), tryptophan hydroxylase 1 (TPH1) and 5-HT transporter (SERT) in colon tissues were detected by Western blot. The contents of substance P (SP) and vasoactive intestinal peptide (VIP) in serum were detected by ELISA. The contents of 5-HT in colon tissue and short chain fatty acid (SCFA) in feces were detected by mass spectrometry., Results: Compared with the normal group, the fecal water content, the expressions of 5-HT, 5-HT4R, TPH1 and SERT in colon tissue, the content of serum SP were significantly decreased ( P <0.05), the first black stool de-fecation time, and the content of serum VIP was significantly increased ( P <0.05), the contents of SCFA in feces were significantly decreased except isobutyric acid ( P <0.05) in the model group. Compared with the model group, the fecal water content, the expressions of 5-HT, 5-HT4R, TPH1 and SERT in colon tissues, the contents of acetic acid and butyrate in feces were significantly increased ( P <0.05) in the EA and drug control groups, the first black stool defecation time was decreased ( P <0.05) in the EA and drug control groups, and the content of serum SP was increased and the content of serum VIP was decreased ( P <0.05) in the EA group. Compared with the drug control group, the content of serum VIP was significantly decreased ( P <0.05), and the expressions of TPH1 and SERT in colon tissue were significantly increased ( P <0.05) in the EA group., Conclusion: EA at BL33 and BL34 can promote intestinal motility by intervening multiple links of 5-HT signaling system in treating STC.

Objective: To explore the role of 5-hydroxytryptamine (5-HT) in type 2 diabetes mellitus (T2DM)-related hepatic inflammation and fibrosis., Methods: Male C57BL/6J mice were used to establish T2DM model by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. Then, the mice with hyperglycemia were still fed with high-fat diet for nine weeks, and treated with or without 5-HT 2A receptor (5-HT 2A R) antagonist sarpogrelate hydrochloride (SH) and 5-HT synthesis inhibitor carbidopa (CDP) (alone or in combination). To observe the role of 5-HT in the myofibroblastization of hepa-tic stellate cells (HSCs), human HSCs LX-2 were exposed to high glucose, and were treated with or without SH, CDP or monoamine oxidase A (MAO-A) inhibitor clorgiline (CGL). Hematoxylin & eosin and Masson staining were used to detect the pathological lesions of liver tissue section, immunohistochemistry and Western blot were used to analyze protein expression, biochemical indicators were measured by ELISA or enzyme kits, and levels of intracellular reactive oxygen species (ROS) were detected by fluorescent probe., Results: There were up-regulated expressions of 5-HT 2A R, 5-HT synthases and MAO-A, and elevated levels of 5-HT in the liver of the T2DM mice. In addition to reduction of the hepatic 5-HT levels and MAO-A expression, treatment with SH and CDP could effectively ameliorate liver lesions in the T2DM mice, both of which could ameliorate hepatic injury and steatosis, significantly inhibit the increase of hepatic ROS (H 2 O 2 ) levels to alleviate oxidative stress, and markedly suppress the production of transforming growth factor β1 (TGF-β1) and the development of inflammation and fibrosis in liver. More importantly, there was a synergistic effect between SH and CDP. Studies on LX-2 cells showed that high glucose could induce up-regulation of 5-HT 2A R, 5-HT synthases and MAO-A expression, increase intracellular 5-HT level, increase the production of ROS, and lead to myofibroblastization of LX-2, resulting in the increase of TGF-β1 synthesis and production of inflammatory and fibrosis factors. The effects of high glucose could be significantly inhibited by 5-HT 2A R antagonist SH or be markedly abolished by mitochondrial 5-HT degradation inhibitor CGL. In addition, SH significantly suppressed the up-regulation of 5-HT synthases and MAO-A induced by high glucose in LX-2., Conclusion: Hyperglycemia-induced myofibroblastization and TGF-β1 production of HSCs, which leads to hepatic inflammation and fibrosis in T2DM mice, is probably due to the up-regulation of 5-HT 2A R expression and increase of 5-HT synthesis and degradation, resulting in the increase of ROS production in mitochondria. Among them, 5-HT 2A R is involved in the regulation of 5-HT synthases and MAO-A expression.

To investigate the effect of Rehmanniae Radix on depression-like behavior and monoamine neurotransmitters of chronic unpredictable mild stress(CUMS) model rats. CUMS combined with isolated feeding was used to induce the depression model of rats. The depression-like behavior of rats was evaluated by sucrose preference test, open field test, and forced swim test. Hematoxylin-Eosin(HE) staining was used to investigate the pathological changes of neurons in the CA1 and CA3 area of hippocampus. Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS) was used to detect the contents of 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), 3,4-dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA), norepinephrine(NE), and 3-methoxy-4-hydroxyphenyl glycol(MHPG) in rats. Western blot was used to detect the protein expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), and monoamine oxidase A(MAO-A) in the hippocampus of rats. Compared with the normal group, depressive-like behavior of rats was obvious in the model group. The arrangements of neurons in the CA1 and CA3 area of hippocampus were loose and disorderly. The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in the hippocampal area were decreased(P&lt;0.01). The protein expression of TPH2 was decreased(P&lt;0.01), but those of SERT and MAO-A were increased(P&lt;0.01). In the Rehmanniae Radix groups with 1.8 g·kg~(-1) and 7.2 g·kg~(-1), the depression-like behavior of CUMS rats and pathological changes of neurons in CA1, CA3 area of hippocampus were improved. The protein expression of TPH2(P&lt;0.05, P&lt;0.01) was increased, and those of SERT and MAO-A were down-regulated(P&lt;0.05, P&lt;0.01). The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in hippocampus were increased(P&lt;0.05, P&lt;0.01). The changes in DA, DOPAC, HVA, DA/(DOPAC +HVA), NE, DHPG, and NE/DHPG were not statistically significant. The results suggested that Rehmanniae Radix improved depression-like behavior of CUMS rats, and the mechanism might be related to the regulation of synthesis, transportation, and metabolism of 5-HT neurotransmitter in the hippocampus.

Based on the brain-gut axis, the present study investigated the effect of Huanglian Houpo Decoction(HLHPD) in the treatment of ulcerative colitis(UC) and explored the mechanism in the regulation of 5-hydroxytryptamine(5-HT), substance P(SP), and vasoactive intestinal peptide(VIP) using modern technologies and molecular docking. Sixty male C57 BL/6 J mice were randomly divided into a blank control group, a model group, a sulfasalazine(SASP) group, and high-(5.00 g·kg~(-1)), medium-(2.50 g·kg~(-1)), and low-dose(1.25 g·kg~(-1)) HLHPD groups. The UC model was induced by oral administration of water containing 3% dextran sulfate sodium salt(DSS) in mice except those in the blank control group. After HLHPD was administered for 10 days, the mice were sacrificed for sample collection. Morphological changes of colon tissues were observed by HE staining. The expression of 5-HT, SP, VIP, tumor necrosis factor α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β) in the hypothalamus, serum, and colon was determined by the enzyme-linked immunosorbent assay(ELISA). The expression of tryptophan hydroxylase 1(TPH1), SP, and VIP in colon tissues was evaluated by immunohistochemistry. The expression of brain-gut peptide receptors, such as 5-HT3 A, neurokinin receptor 1(NK-1 R), and VIP receptor 1(VPAC1) in colon tissues was investigated by Western blot. The binding affinity of the brain-gut peptide receptors to the main components of HLHPD was analyzed by molecular docking. After HLHPD intervention, UC mice showed increased body weight, reduced DAI score and occult blood, prolonged colon, down-regulated levels of TNF-α, IL-1β, and IL-6 in colon tissues, and relieved pathological damage in the colon. The VIP levels in the colon were significantly up-regulated in the HLHPD groups. The high-and medium-dose HLHPD could significantly down-regulated SP and 5-HT in colon tissues and 5-HT in the serum, and up-regulated the VIP in the serum. The high-dose HLHPD group could down-regulate 5-HT and up-regulate VIP in the hypothalamus. It is suggested that HLHPD can reverse the levels of brain-gut peptides in UC mice to varying degrees. Correlation analysis results suggested that the expression levels of brain-gut peptides in the hypothalamus, serum, and colon tissues were related to inflammatory factors. Molecular docking results showed that berberine, coptisine, and epiberberine were presumedly the material basis for HLHPD in regulating the levels of 5-HT3 A, NK-1 R, and VPAC1. The main components of HLHPD may reduce colonic inflammation and pathological damage of colon tissues by regulating the activity of brain-gut peptides and their receptors, thereby reducing DSS-induced colitis in mice.

Objective: Sepsis has the characteristics of high morbidity and high mortality, which is the main cause of death in critically ill patients. Peripheral 5-hydroxytryptamine (5-HT) is mainly synthesized and secreted by enterochromaffin cells and plays a role in the development and progression of inflammation. This article focuses on 5-HT, 5-HT transporter (SERT) and selective serotonin reuptake inhibitors (SSRIs) in immune response, inflammatory factor release, oxidative stress, intestinal bacterial translocation and microcirculation of sepsis. The role of the review is to find new ideas for the clinical treatment of sepsis.

This study is to investigate the effect of antidepressant medicine prescription Dingzhi Xiaowan (DZ) on miR-16 expression levels in vitro and in vivo, and to explore the mechanism of DZ elevated levels of 5-HT from the perspective of post transcriptional regulation. Firstly, a chronic unpredictable mild moderate stimulation (CUMS) combined with solitary rising depression rat model was established, the behavior changes were detected after different doses of DZ (600, 300, 150 mg·kg⁻¹) given for 3 weeks, high performance liquid chromatography (HPLC) was used to detect 5-HT level in hippocampal, PCR method was used to observe the effect of DZ on the expression of SERT mRNA and miR-16 in hippocampus of CUMS rat. The effects of DZ (10, 100, 200, 500 mg·L⁻¹) on the expression of miR-16 and SERT mRNA in the cell model induced by miR-16 silencing and corticosterone or glutamate injury were observed in primary cultured hippocampal neurons of rats in vitro. It was found that 300 mg·kg⁻¹ and 600 mg·kg⁻¹ DZ could significantly improve the behavioral score of CUMS rats, increase the level of 5-HT in hippocampus, and increase the expression of miR-16 and decrease the expression of SERT in the hippocampus of rats. At the same time, in primary cultured hippocampal neurons, 100, 200, 500 mg·L⁻¹ of DZ could significantly increase the expression level of miR-16 in miR-16 silencing and corticosterone or glutamate injury cell model, and decrease the expression level of SERT significantly. So DZ could inhibit the reuptake of 5-HT by inhibiting the expression of SERT by up regulating the expression level of miR-16, and finally increase the level of 5-HT in the brain and exert antidepressant effect., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To observe the intervention effect of Qiaoshao Prescription (QSP) on premature ejaculation (PE) induced by 8-OH-DPAT in male rats and explore its possible action mechanism., Methods: Seventy-two male Wistar rats were equally randomized into six groups, blank control, PE model control, low-, medium- and high-dose QSP, and dapoxetine. The PE model was established by injection of 8-OH-DPAT into the subarachnoid space of the lumbosacral spinal cord. Four weeks after modeling, the rats in the blank control and PE model control groups with gavaged with normal saline at 10 ml/kg/d, those in the low-, medium- and high-dose QSP groups with QSP at 5, 10 and 20 g/kg/d respectively once a day, and those in the dapoxetine group with dapoxetine hydrochloride at 300 mg/kg at 3 hours before mating. Forty-five female Wistar rats were injected subcutaneously with 20 μg estradiol benzoate after removal of bilateral ovaries to induce estrous estrus. Two and 4 weeks later, the male rats were mated with the female ones for 30 minutes per time and meanwhile observed for the mating behavior of the males, including mounting latency (ML), intromission latency (IL), ejaculation latency (EL), mounting frequency (MF), intromission frequency (IF), and ejaculation frequency (EF). After the 4th week of mating, the hypothalamus of the animals was isolated and weighed, and the content of 5-hydroxytryptamine (5-HT) was measured., Results: Compared with the blank control group, the PE model controls showed significantly decreased content of 5-HT in the hypothalamus(1 257.1 vs 923.4 ng/g, P<0.05), ML (［11.22 ± 3.60］ vs ［8.69 ± 2.48］ s, P<0.05), IL (［22.33 ± 2.45］ vs ［12.08±1.39］ s, P<0.05), MF (［13.28 ± 3.24］ vs ［7.53 ± 1.84］ times, P<0.05), and EL (［712.35 ± 36.77］ vs ［502.35 ± 46.72］ s, P<0.05). In comparison with the PE model controls, the rats of the QSP and dapoxetine groups exhibited remarkably increased content of 5-HT (P<0.05) and prolonged EL (P<0.05)., Conclusions: Qiaoshao Prescription can prolong EL in PE rats, which might be associated with the increased content of 5-HT in the hypothalamus. Further studies, however, are needed on its underlying mechanisms.

Objective To investigate the changes of 5-HT (serotonin) signaling system in allergic diarrhea mice sensitized with ovalbumin (OVA). Methods The seven-to-eight-week-old BALB/c female mice were randomly divided into model group, sodium chromate group and negative control group. The model group and sodium chromate group were intraperitoneally injected with OVAI (50 μg per mouse) at day 0 and day 14 respectively. And starting from the 28th day, OVAII was orally administered (50 mg per mousee) every other day (8 times in total), and the sodium chromate group was given the sodium chromate (78.0 mg/kg) before the oral administration of OVA every other day (8 times in total). The allergic symptoms, including the systemic score, faeces score and body temperature were recorded following the OVA administration for sensitization. The mice were executed 43 days later. Eyeball blood sample was collected, and then serum was seperated by centrifugation, the gastric tissues was taken out. The serum OVA-specific IgE (OVA-SIgE) was detected by ELISA. The serum content of 5-HT and its related metabolites including kynurenine (KYN), tryptophan (TRP), 5-hydroxytryptophan (5-HTP), and 5-hydroxyindoleacetic acid (5-HIAA) were examined by liquid chromatography-mass spectrometry (LC-MS). The mRNA levels of tryptophan hydroxylase-1 (TPH1), indolamine-2, 3-dioxygenase 1 (IDO1), monoamine oxidase A (MAO-A), 5-hydroxytryptamine 1A receptor (HTR1A), 5-hydroxytryptamine 3 receptor (HTR3), 5-hydroxytryptamine 4 receptor (HTR4) and serotonin reuptake transporter (SERT) were determined by real-time quantitative PCR. Results OVA sensitization caused severe allergic diarrhea in mice. Serum OVA-SIgE increased significantly in mice sensitized by OVA. serum KYN increased remarkably, while 5-HT, 5-HIAA and 5-HTP decreased significantly. The mRNA levels of IDO1, HTR1A and HTR3A increased in gastric tissues, while the levels of TPH1 and MAO-A mRNA decreased. Compared with the model group, the sodium chromate group had lowed systemic score, faeces score, body temperature and OVA-SIgE as well as diarrhea rate. The mRNA levels of 5-HIAA and MAO-A increased in the gastric tissues, and IDO1, 5-HT1A and 5-HT3A mRNAs decreased in the sodium chromate group. Conclusion The serotonin signaling system in ovalbumin-sensitized allergic diarrhea mice has been activated. The administration of sodium chromate can alleviate the allergic symptoms, and change the levels of serum metabolites and the gene expressions of the 5-HT metabolic pathway and its receptors in the stomach.

This study aimed to investigate the effects of baldrinal of Valeriana jatamansi on the expression of corticotropin releasing factor (CRF) and tryptophan hydroxylase 1 (TPH1) mRNA and levels of 5-hydroxytryptamine (5-HT) in colon of rats with irritable bowel syndrome (IBS), and to explain its therapeutic mechanism on IBS through 5-HT pathway. Fifty-four male SD rats were randomly divided into 6 groups: blank group, model group, baldrinal high, medium and low dose groups, and pinaverium bromide group, n=9 in each group. The IBS rat models were established by using unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest and independent feeding. CRF expression was detected by IHC-P; TPH1 mRNA expression was detected by using RT-PCR and the 5-HT level was measured by high performance liquid chromatography(HPLC). The results indicated that the method of chronic stress with acute restrain stress method and independent feeding could lead to the increase in expressions of CRF and TPH1 mRNA and levels of 5-HT in IBS rats(P<0.05). The expressions of CRF, TPH1 mRNA and 5-HT in baldrinal groups were significantly lower than those in model group(P<0.05). The experimental results showed that IBS could result in increase in the expressions of CRF, TPH1 mRNA and levels of 5-HT, and the baldrinal of V. jatamansi could improve the symptoms of IBS by reducing the expressions of CRF, TPH1 mRNA and levels of 5-HT in colon of rats., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Electroacupuncture (EA) has been demonstrated effective for pain relief. However, repeated application may decline analgesic effect of EA, which is termed EA tolerance, that reduces the clinical efficacy of EA. Therefore, it has attracted attention from researchers in recent years and the progresses include:(1) acute and chronic EA tolerance animal models have been established; (2) cross-tolerance between EA and morphine; (3) Anti-opioid substances, including cholecystokinin, orphanin FQ and angiotensin Ⅱ, have been reported to contribute to EA tolerance; (4) glutamate receptors and transporters, 5-hydroxytryptamine and norepinephrine have been revealed involvement in EA tolerance; (5) cyclic adenosine monophosphate, cyclic guanosine monophosphate and Ca 2+ have been reported to be the second messengers cellularly in EA tolerance. The current EA tolerance effect lacks in-depth researches. Therefore, studies on its molecular mechanisms and signaling pathway are necessarily required.

Objective: To observe the effect of manual acupuncture intervention on serotonin transporter (5-HTT), 5-HT 1 A receptor (5-HT 1A R), norepinephrine (NE) alpha receptor 2 (NEα 2 R) protein of brain tissues in rats with post-stroke depression (PSD)., Methods: Forty SD rats were randomly divided into normal group, model group, medication group and acupuncture group, with 10 rats in each. The PSD model was established by the combination of middle cerebral artery occlusion and chronic non- predictable mild stress. Rats of the medication group were treated by gavage of fluoxetine (2 mg/kg, once daily for 21 days), and those of the acupuncture group treated by manual acupuncture stimulation of "Baihui"(GV 20), "Fengfu" (GV 16), bilateral"Shenmen" (HT 7) and "Taichong" (LR 3) for 20 min, once a day for 21 days, with one day's interval between each every 7 days. The animals' neurological deficit was detected by Zea Longa's scaling, and the depression status assessed by sugar solution consumption, and the locomotor activity (crossing and rearing times in 5 min) detected by open-field tests. The contents of 5-HT, NE, acetylcholine (ACh), gamma aminobutyric acid (GABA), and glutamate (Glu) of the cerebral cortex were detected using high performance liquid chromatography (HPLC) and expression levels of 5-HTT, 5-HT 1A R, NEα 2 R proteins of the hippocampus, raphe nuclei and locus coeruleus(LC) tissues detected using western blotting (EB), respectively., Results: After modeling, the neurological deficit score was significantly increased, while the sugar solution consumption and the locomotor activities (crossi-ng and rearing times in 5 min) were notably decreased ( P <0.05, P <0.001). Findings of HPLC and WB indicated that after modeling, the cerebrocortical 5-HT and NE contents and 5-HTT protein expression levels in the hippocampus, raphe nucleus and LC were obviously decreased and the cortical ACh, GABA and Glu contents as well as the expression of 5-HT 1A R and NEα 2 R proteins in the hippocampus, raphe nucleus and LC considerably increased in the model group ( P <0.01). Following acupuncture intervention and medication, the increased neurological deficit score, cortical ACh, GABA and Glu contents, and the expression le-vels of 5-HT 1A R and NEα 2 R proteins in the hippocampus, rahpe nucleus and LC, as well as the decreased sugar solution consumption, crossing and rearing times of open field tests, cortical 5-HT and NE contents, as well as cortical 5-HT protein expression were all reversed in both acupuncture and medication groups ( P <0.05, P <0.01). No significant differences were found between the acupuncture and medication groups in all the above-mentioned indexes ( P >0.05)., Conclusions: Acupuncture can improve the locomotor function changes in stroke rats with depression after stroke, which may be associated with its effects in suppressing the up-regulated cortical ACh, GABA, Glu contents, the expression levels of 5-HT 1A R and NEα 2 R proteins in the hippocampus, raphe nucleus and LC, and the down-regulated 5-HT and NE contents in the cerebral cortex and 5-HTT protein expression levels in the hippocampus, raphe nucleus and LC.

Objective: To investigate the effects of Liuwei Dihuang (LWDH) decoction on serotonine (5-HTs), melatonin and the activity of the rate-limiting enzymes ANNAT and HIOMT in cultured human melanocytes and in melanocytes co-cultured with keratinocytes., Methods: CCK-8 assay was used to assess the proliferation of melanocytes and melanocytes co-cultured with keratinocytes after treatment with the serum from rabbits fed with LWDH decoction. High-performance liquid chromatography was used to determine 5-HT and melatonin contents, and real-time fluorescent PCR was employed to evaluate the ANNAT and HIOMT activities in the cell cultures., Results: The serum from rabbits fed with LWDH Decoction at low doses did not affect the proliferation of melanocytes co-cultured with keratinocytes, but at the concentrations of 20%-40%, the serum significantly inhibited the proliferation of melanocytes, and the effect was optimal with a concentration of 40% (P<0.05). 5-HT and melatonin contents in the cell culture decreased as the serum concentration increased (P<0.05), which was the most obvious with a serum concentration of 40% (P<0.01). Exposure of the cells to low and moderate doses of the serum caused a dose-dependent decrease in AANAT activity (P<0.05), but the serum produced no significant changes in the level of HIOMT mRNA expression in the cells., Couclusions: The serotoninergic/melatoninergic system mediate the regulation of melanin metabolism by LWDH Decoction, the mechanism of which may involve 5-HTs, melatonin and ANNAT.

Objective: To evaluate the effect of ginsenoside pre-treatment on serotonin (5-hydroxytryptamine, 5-HT), 5-HT2A receptor (5-HT2AR), and 5-HT transporter (serotonin transporter, SERT) in serum, platelet lysate and brain tissue homogenates in SD rats with myocardial infarction (MI) or depression., Methods: Eighty SD rats were randomized treated with ginsenoside or normal saline(NS). After 4 weeks, the rats were, then, randomized to four subgroups: the MI, the depression, the MI in combination with depression and sham subgroups.5-HT, 5-HT2AR and SERT levels were detected in serum, platelet or brain., Results: In the NS pre-treatment groups, serum 5-HT levels in sham rats (237.1±32.0) pg/ml were higher than in MI (58.0±11.6) pg/ml, depression (72.8±2.3) pg/ml, and MI with depression rats (62.5±10.2) pg/ml (all P=0.000). Pre-treatment of ginsenoside increased serum and platelet 5-HT in MI, depression and MI with depression rats compared with each corresponding NS treated subgroups (all P<0.005). However, treatment of ginsenoside lowered the 5-HT2AR expression in MI, depression, and MI with depression subgroups both in platelet and brain tissue homogenates compared with each corresponding NS treated subgroups (all P<0.05). As to SERT in platelet, treatment of ginsenoside increased its levels in depression rats (P=0.019), but lowered the levels in MI rats (P=0.001) compared with NS treated rats.There were no differences in brain 5-HT and SERT between ginsenoside and NS treated groups., Conclusions: The 5-HT system responses differently to ginsenoside treatment under different cardiac and mental stress conditions.Ginsenoside plays an important role in regulation of 5-HT system.

Objective: To explore the effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking on auditory brainstem response (ABR) and contents of neurotransmitters of γ-aminobutyric acid (γ-GABA), 5-hydroxytryptamine (5-HT) and acetyl choline (Ach) in inferior colliculus of tinnitus rats., Methods: Twenty-four male adult SD rats were randomized into a control group, a model group, a 7-d treatment group and a 15-d treatment group. Except the control group, rats in the remaining groups were treated with intraperitoneal injection of 10% salicylate sodium at a dose of 350 mg/kg to establish tinnitus model. Rats in the control group were treated with injection of 0.9% NaCl. Rats in the 7-d treatment group and 15-d treatment group were treated with electrical stimulation at "Shenmen (TF₄)" and "Yidan (CO₁₁)" in the distribution area of auricular vagus nerve combined with sound masking, once a day, for 7 days and 15 days. The SigGenRP software of TDT system was applied to provide voice for single ear and collect the signal, and the voice threshold of ABR was tested. The levels of γ-GABA, 5-HT and Ach in inferior colliculus of rats were detected by enzyme linked immunosorbent assay (ELISA) and compared., Results: Compared with the model group, the threshold values of ABR in 12 kHz and 16 kHz voice stimulation in the 7-d treatment group were significantly lower all P < 0.05); the threshold values of ABR from 4 kHz to 28 kHz voice stimulation in the 15-d treatment group were signally reduced (P < 0.05, P < 0.01), which was more significant than those in the 7-d treatment group. The level of γ-GABA in the model group was significantly lower than that in the control group (P < 0.05), and that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of 5-HT in the model group was markedly higher than that in the control group (P < 0.05), and that in the 7-d treatment group was lower than that in the model group (P < 0.05), while that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of Ach in the model group was obviously; lower than that in the control group (P < 0.05), and that in the 7-d treatment group was higher than that in the model group (P < 0.05)., Conclusion: Electrical stimulation at auricular vagus nerve combined with sound masking) could regulate the threshold of ABR, especially in the 15-d treatment group. This may be ascribed to modulating the levels of neurotransmitter of γ-GABA, 5-HT and Ach in inferior colliculus.

In the paper, by taking acupuncture and migraine as the key words to retrieve CNKI and PubMed database, the literature analysis was done on the mechanism study on experimental migraine treated with acupuncture in rat model. The results showed that acupuncture mechanism study focused on the regulation and control of the relevant neurotransmitters/neuromodulators of migraine, such as calcitonin gene-related peptide (CGRP), serotonin (5-HT), nitric oxide (NO), etc. Moreover, in the paper, the review had been done on the neurotransmitters/neuromodulators involved in the study.

Objective: To observe the effect of acupuncture and moxibustion interventions on ethology and 5-HT/5-HIAA levels in the frontal cortex tissue in depression rats, so as to reveal their biological mechanisms underlying improvement of depression., Methods: A total of 40 male SD rats were randomized into normal control, depression model, medication (Fluoxetine), acupuncture and moxibustion groups, with 8 rats in each group. The depression model was established by chronic unpredictable mild stress for 5 weeks. The interventions including acupuncture or moxibustion stimulation of "Baihui" (GV 20) and "Dazhui" (GV 14) for 20 min/d and intragastric administration of Fluoxetine (1.8 mg · kg⁻¹ · d⁻¹) beginning after 2 weeks of modeling for 3 weeks. The percentages of sucrose consumption was counted, the contents of 5-HT, hydroxyindole acetic acid (5-HIAA), tryptophan (Trp) in the prefrontal cortex tissue were assayed by radioimmunoassay, and the relative binding affinities (constant and capacity) of 5-HT1A receptor in the prefrontal cortex were measured by radioligand binding assay and Scatchard plot analysis in a computer. Results In comparison with the normal control group, the sucrose consumption percentage on the 35th day of modeling, the levels of cerebral cortical 5-HT, 5-HT/5-H1AA and 5-HT1A receptor binding constant were significantly down-regulated in the model group (P < 0.01, P < 0.05), and the cortical Trp content was obviously up-regulated in the model group (P < 0.01). Compared with the model group, the sucrose consumption percentage on the 35th day of modeling, and cortical 5-HT/5-HIAA in the medication, acupuncture and moxibustion groups, cortical 5-HT content in the medication group were significantly increased (P< 0.01, P < 0.05), and cortical 5-HIAA and Trp contents were obviously down-regulated in the three treatment groups (P < 0.01). No significant changes were found in the cortical 5-HT content after acupuncture and moxibustion, and in the high and lower affinity of 5-HTA receptor binding constant and binding capacity after medication, acupuncture and moxibustion interventions (P > 0.05). The effects of acupuncture and moxibustion interventions were comparable in increasing sucrose consumption percentage on the 35th day and 5-HT/5-HIAA, and in down-regulating cortical Trp content (P > 0.05)., Conclusion: Both acupuncture and moxibustion can increase sucrose consumption (anti-depression) in depression rats, which may be closely associated withheir effects in up-regulating 5-HT/5-HIAA and down-regulating Trp content in the frontal cortex.

Objective: To observe the influence of herbal cake-separated moxibustion on the contents of 5-hydroxy tryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the hypothalamus in rats with functional dyspepsia (FD) of syndrome of liver stagnation and spleen deficiency, so as to explore its mechanism underlying improvement of FD., Methods: Sixty SD rats were randomly divided into 6 groups: control, model, herbal cake-separated moxibustion, moxa-cone moxibustion, Xiaoyaosan (decoction for relieving liver stagnation) and Domperidon, with 10 rats in each group. The FD model was established by applying chronic restraint stress + excessive fatigue + irregular food + tail clipping+ shaking for 21 consecutive days. Moxibustion (herbal cake-separated or moxa-cone) was applied to bilateral "Ganshu" (BL 18), "Pishu" (BL 20) and "Weishu" (BL 21), or "Zhangmen"(LR 13), "Qimen" (LR 14) and "Zhongwan" (CV 12) for 30 min, once daily for 14 d. For rats of the two medication groups, Xiaoyaosan [1 mL (2 g)/100 g] and Domperidone [1 mL (0.3 g)/100 g] were administrated by gavage, respectively. The contents of 5-HT, DA and NE in the hypothalamus tissue were detected by high performance liquid Phrnm.tnrnh,, Results: The gastric empty rate was obviously lower in the model group than in the control group (P<0. 01). After the treatment, the gastric empty rate in the herbal cake-separated moxibustion, moxa-cone moxibustion, Xiaoyaosan and Domperidone groups were significantly increased in comparison with the model group ( P<0. 01) , but there were no significant differences among the four treatment groups (P > 0.05). Compared to the control group, the contents of 5-HT, DA and NE in the hypothalamus were markedly decreased in the model group (P < 0.01), while compared to the model group, the contents of hypothalamic 5- HT, DA and NE contents were significantly up-regulated in both the herbal cake-separated moxibustion and Xiaoyaosan groups (P < 0.01), rather than in the moxa-cone moxibustion and Domperidone groups (P > 0.05). No significant differences were found between the herbal cake-separated moxibustion and Xioayaosan groups in increasing hypothalamic 5-HT, DA and NE levels (P > 0.05)., Conclusion: Herbal cake-separated moxibustion can promote the gastric empty rate in FD rats, which may be associated with its effects in inhibiting stress induced decrease of hypothalamic 5-HT, DA and NE levels.

Objective: To screen the effective acupoints for anti-depression in depression rats and to explore the mechanisms of acupuncture for relieving depression., Methods: Fifty rats were randomly divided into normal control, model, "Yin-tang" (EX-HN 3)-"Baihui" (GV 20, 2-acupoints), EX-HN 3-GV 20-"Fengchi" (GB 20)-"Shenshu" (BL 23, 4-acupoints) and medication groups, with 10 rats in each group. The depression model was established by unpredictable chronic mild stress (UCMS) for 28 days. For rats of the 2-acupoints and 4-acupoints groups, EX-HN 3 and GV 20, and EX-HN 3, GV 20, GB 20 and BL 23 were punctured with filiform needles respectively before performing mild stress every time. The acupuncture needles were retained for 30 min during each intervention and the treatment was conducted once daily for 28 days. The rats of the medication group were treated by intragastric administration of Fluoxetine (0.18 mg/kg) once a day for 28 days. The rats' anxiety-like behavior (rearing and crossing times) was detected by open-field test. The contents of adrenocorticotropic hormone (ACTH) in the pituitary, 5-hydroxytryptamine (5-HT) in the hippocampus, the cortisol (CORT) in the adrenal gland, and the brain derived neurotrophic factor (BDNF) in the serum were examined by ELISA., Results: Compared to the normal control group, the numbers of both rearing and crossing motions in the model group were significantly decreased (P<0.01, P<0.05), while in comparison with the model group, the rearing and crossing numbers of rats in the 2-acupoints and 4-acupoints and medication groups were significantly increased (P<0.01). ELISA showed that after modeling, the content of adrenal CORT was significantly increased (P<0.01), and those of hippocampal 5-HT and serum BDNF were obviously down-regulated in the model group (P<0.01). After the treatment, the adrenal CORT levels in the three intervention groups were notably down-regulated, and hippocampal 5-HT and serum BONE evidently up-regulated in these 3 intervention groups (P<0.05, P<0.01). No marked changes were found in the pituitary ACTH contents of the model and 3 intervention groups (P>0.05), and no significant differences were shown among the three intervention groups in the levels of the aforementioned 6 indexes (P>0.05)., Conclusion: Acupuncture intervention can effectively improve the unprompted activates of the depression rats, which may be related to its effects in up-regulating hippocampal 5-HT and serum BONE levels, and in down-regulating adrenal CORT content.

Objective: To explore the change pattern of hypothalamic-pituitary-adrenal (HPA) axis and related neurotransmitters under simulated weightlessness., Methods: A total of 40 clean-grade male Wistar rats were randomly divided into a normal group, a tail-suspension group, an electroacupuncture (EA) at Neiguan (PC 6) group, an EA at Sanyinjiao (SP 6) group, 10 rats in each group. Rats in the tail-suspension group, EA at "Neiguan" (PC 6) group and EA at "Sanyinjiao" (SP 6) group were treated with tail suspension to simulate weightlessness effect. Rats in the normal group were treated with normal diet. Rats in the tail-suspension group were treated with tail suspension for 28 d. During the time of tail suspension, rats in the EA at "Neiguan" (PC 6) group were treated with EA at "Neiguan" (PC 6), 30 min per treatment, once every two days for 14 treatments, while rats in the EA at "Sanyinjiao" (SP 6) group were treated with EA at "Sanyinjiao" (SP 6), 30 min per treatment, once every two days for 14 treatments. Samples were all collected after 4 weeks. The contents of corticotropin releasing hormone (CRH) , adrenocorticotropic hormone (ACTH), corticosterone (CORT) in as well as 5-hydroxy tryptamine (5-HT), dopamine (DA), norepinephrine (NE) were measured by using radioimmunoassay., Results: Compared with the normal group, in the tail-suspension group the content of ACTH in pituitary was significantly decreased (P< 0.05), and the content of 5-HT in hypothalamus was significantly decreased (P < 0.01); the content of CRH and 5-HT in hypothalamus was significantly decreased (P < 0.01, P < 0.05) in the EA at "Neiguan" (PC 6) group; the content of CRH and 5-HT in hypothalamus was significantly decreased (P < 0.01), and the content of CORT in serum was significantly decreased (P < 0.05) in the EA at "Sanyinjiao" (SP 6) group. Compared with the tail-suspension group, the content of ACTH in hypothalamus was significantly decreased (P< 0.05) in the EA at "Neiguan" (PC 6) group; the content of CRH, ACTH and CORT was significantly decreased (P < 0.01, P < 0.05) in the EA at "Sanyinjiao" (SP 6) group. Compared with the EA at "Neiguan" (PC 6) group, the content of CORT was decreased (P < 0.05) in the EA at "Sanyinjiao" (SP 6) group., Conclusion: EA can regulate the content of 5-HT in hypothalamus in tail-suspension rats, inhibit the hyperactivity of the HPA axis, in which EA at "Sanyinjiao" (SP 6) had more significant effects than "Neiguan" (PC 6), but no obvious effects on NE and DA were observed.

The present study aims to investigate the kinetic histocytochemical changes of acupoints in different condition. The expression of tryptase (+) mast cells, histamine (HA) , serotonin (5-HT) and nociceptive neuropeptides including calcitonin gene-related peptide (CGRP) and substance P (SP) were observed by immunohistochemistry combined with confocal technology. Mast cells were labeled with anti-mast cell tryptase antibody and simultaneously with HA or 5-HT primary antibodies to observe their co-expression. The results showed that: (1) SP and CGRP were expressed more highly on the cutaneous nerve fibers of "Hegu" (LI 4) after acupuncture stimulation than that of the control. Mast cells aggregated in close proximity to the blood vessels in intra-epidermis and dermis, and some of them with degranulation in the lower dermis and subcutaneous tissue of "Hegu" (LI 4). Both mast cells and their granules appeared with HA (+) and 5-HT (+) expression at stimulated LI 4 sites, while a few intact mast cells with a little expression of 5-HT and HA were distributed in areas of non-stimulated Ll 4. (2) The acupoints in different locations such as Baihui (GV 20), Weishu (BL 21), Zhongwan (CV 12) and LI 4 had the same constituent but the contents were different. (3) The histocytochemical responses of acupoints sensitized by the Gastric mucosa injury (GMI) were also investigated. GMI resulted in neurogenic plasma extravasation by Evans Blue (EB) in the skin of the acupoints over the back and abdomen, which mostly occurred in the T9-T11 dermatomere. The EB extravasation dots just like acupoints sensitization appeared after GMI and disappeared gradually during the natural self-recovery of the gastric mucosa. More SP and CGRP positive nerve fibers were distributed in EB dots than in regions beside EB dots and in the control, mostly distributed in the nerve fibers around both the vessels and root of hair follicle. Mast cells also aggregated and degranulated to release algogenic substances of 5-HT and HA around the vessels in areas of the EB dots. Collectively the acupoints displayed the same histocytochemical responses due to either acupuncture stimulation or GMI. This may potentially be the histocytochemical basis in the local acupoints and acupoints displayed kinetic changes in different condition.

Objective: To explore the effect of Chang'an No. I Recipe (CA) on 5-hydroxytryptamine signal system and mRNA expression levels of hippocampal brain derived neurotrophic factor (BDNF) in visceral hypersensitivity model rats with irritable bowel syndrome (IBS)., Methods: IBS visceral hypersensitivity rat models were established by combined chronic restraint stress and forced swimming. Successfully modeled rats were randomly divided into the model group, the Dicetelgroup (27 mg/kg) , the Fluoxetine group (3.6 mg/kg), the high dose CA group (22.6 mg/kg), the medium dose CA group (11.3 mg/kg), and the low dose CA group (5.7 mg/kg) according to body weight, 9 in each group. Besides, a normal control group with 10 rats was set up. Corresponding medication was administered to rats in each treatment group. Equal volume of physiological saline was administered to rats in the model group by gastrogavage. All medication was performed once per day for a total of 14 days. Pain threshold was determined by abdominal withdrawal reflex (AWR). Changes of colon 5-HT levels were determined by immunohistochemical assay. mRNA expression levels of hippocampal 5-hydroxytryptamine 1A receptor (5-HT1a) and BDNF were detected by immunofluorescent RT-PCR., Results: Compared with the normal control group before treatment, pain threshold was obviously lowered in proctectasia rats of each group (P < 0.01). Compared with the normal control group after treatment, pain threshold was obviously lowered in rats of the model group; colon 5-HT levels, mRNA expression levels of hippocampal 5-HT1a and BDNF were obviously elevated (P < 0.01). Compared with the model group, pain threshold was obviously elevated in the Fluoxetine group and all CA groups; colon 5-HT levels were obviously reduced in the Dicetel group, high and medium dose CA groups (P < 0.05, P < 0.01); mRNA expression levels of hippocampal 5-HT1a and BDNF were obviously reduced in each CA group (P < 0.01); mRNA expression levels of hippocampal BDNF were obviously reduced in the Fluoxetine group (P < 0.01)., Conclusions: The target points of CA were involved in brain and gut. CA could reduce pain threshold of proctectasia rats, down-regulate colon mucosal 5-HT levels, and lower mRNA expression levels of BDNF and 5-HT1a in rat hippocampus.

Objective: To observe the effect of electroacupuncture (EA) stimulation of "Yifen" (TE 17), "Shenshu" (BL 23) on the expression of 5-hydroxytryptamine receptor 1 B (5-HTR 1 B) mRNA and 5-hydroxytryptamine receptor 2 C (5-HTR 2 C) mRNA in the cochlear nucleus tissue in mice experiencing radiation from mobile phone, so as to explore its mechanisms underlying improvement of tinnitus., Methods: Thirty Kunming mice were randomly divided into control group (n = 6) and modeling group (n = 24). The tinnitus model was established by giving the mice with mobile phone-radiation for 1 h in the morning and 1 h in the afternoon, continuously for 40 days. EA stimulation was applied to "Yifeng" (TE 17) group (n = 6) and "Shenshu" (BL 23) group (n = 6) for 20 min, once a day for 7 days. The expression of 5-THR 1 B/2 C mRNA in the cochlear nucleus was assayed by fluorescence quantitative polymerase chain reaction (real time-PCR)., Results: The expression level of 5-HTR 1 B was significantly lower in the model group than in the control group (P < 0.05), while that of 5-HTR 2 C mRNA significantly increased (P < 0.01). TE 17 group received a significant acupoint intervention effect (P < 0.01). Compared with TE 17 group, BL 23 group received a weaker effect (P < 0.05)., Conclusion: EA of TE 17 can up-regulate expression level of 5-HTR 1 B and down-regulate expression level of 5-HTR 2 C in the cochlear nucleus in mice experiencing mobile-phone radiation.

Objective: To compare the difference in the efficacy between acupuncture and oral administration of trazodone and the expressions of neurotransmitters in patients of insomnia differentiated as liver stagnation transforming into fire., Methods: Seventy patients of insomnia differentiated as liver stagnation transforming into fire were randomized into an observation group and a control group, 35 cases in each one. In the observation group, acupuncture therapy was adopted at Shenmen (HT 7), Baihui (GV 20), Yintang (GV 29), Hegu (LI 4), Taichong (LR 3), etc. The needles were retained for 20 min each time. The treatment was given once a day, the treatment of 2 weeks made one session. In the control group, trazodone, 100 mg, oral administration, once a day, the treatment of 2 weeks made one session. Two sessions were required in the two groups. The scores in Pittsburgh sleep quality index (PSQI) and Asberg rating scale for side effects (SERS), the levels of neurotransmitters such as 5-hydroxy tryptamine (5-HT) and norepinephrine (NE) and the expressions of protein kinase C (PKC) and brain-derived neurotrophic factor (BDNF) in peripheral blood were observed before and after treatment in the two groups., Results: PSQI score and SERS score after treatment were all decreased compared with those in both groups before treatment (both P<0. 05). After treatment, PSQI score and SERS score in the observation group were lower apparently than those in the control group (both P<0. 05). After treatment NE content and PKC level were decreased; 5-HT content and BDNF mRNA were increased compared with those in both groups before treatment (all P<0. 05). NE content and PKC level in the observation group were lower apparently than those in the control group (both P<0. 05). The serum 5-HT content and BDNF mRNA expression in the observation group were higher than those in the control group separately (both P<0. 05)., Conclusion: Acupuncture therapy improves the sleeping quality of patients of insomnia differentiated as liver stagnation transforming into fire, and reduces serum NE level and increases 5-HT content and BDNF expression, which achieves the better efficacy as compared with the oral administration of trazodone. It is one of the effective approaches to the treatment of insomnia differentiated as liver stagnation transforming into fire.

Objective: To explore the effect of inherent depression on chronic visceral hypersensitivity. The differences of visceral sensitivity, colitis, and brain activation between Fawn-Hooded (FH/Wjd) and Sprague-Dawley(SD) rats were identified after neonatal colon acetate stimulation., Methods: The specific pathogen free Fawn-Hooded (FH/Wjd) and Sprague-Dawley(SD) rats were used to establish irritable bowel syndrome (IBS) model. The visceral sensitivity was measured by colorectal distension (CRD). The expression of 5-hydroxytryptamine (5-HT), mast cell (MC), indoleamine 2,3-dioxygenase (IDO) in colon and IDO in specific cerebral regions were detected through immunohistochemistry., Results: Abdominal withdrawal reflex (AWR) scores showed that visceral sensitivity of acetate-enema groups was significantly higher than that of saline-enema groups (FH/Wjd:2.44 ± 0.04 vs.1.96 ± 0.07, P < 0.05; SD: 1.75 ± 0.13 vs.1.32 ± 0.05, P < 0.05). Furthermore, FH/Wjd rats of IBS group scored significantly higher than SD rats of IBS group (2.44 ± 0.04 vs.1.75 ± 0.13, P < 0.05). The MC amounts of both SD and FH/Wjd IBS group rats were significantly more than those of their control groups (FH/Wjd:43.24 ± 1.72 vs. 24.92 ± 1.38, P < 0.01. SD: 23.80 ± 1.28 vs. 14.24 ± 0.92, P < 0.01). Besides, the MC amounts of control and IBS group of FH/Wjd rats were significantly more than that of SD IBS group rats (P < 0.01). The IDO and 5-HT positive cells in colonic mucosa of IBS group of both SD and FH/Wjd rats were significantly more than those of their control groups, respectively(P < 0.01). The IDO, 5-HT positive cells in colonic mucosa of both control and IBS group of FH/Wjd rats were significantly more than those of both control and IBS group of SD rats (control:IDO,24.64 ± 2.22 vs. 15.52 ± 1.39;5-HT,21.32 ± 1.26 vs. 12.72 ± 1.12. IBS: IDO,44.92 ± 2.31 vs. 20.85 ± 1.72; 5-HT, 31.84 ± 1.57 vs. 19.65 ± 1.09.P <0.01). The expression of IDO in prelimbic cortex (PrL) areas of FH/Wjd IBS rats was significantly higher than that of IBS group of SD rats (49.60 ± 4.31 vs. 35.60 ± 2.42, P <0.01), and the expression of IDO in rostral anterior cingulate cortex (rACC) areas of FH/Wjd IBS rats was significantly more than that of FH/Wjd control rats (45.44 ± 1.16 vs. 34.08 ± 2.76, P <0.01)., Conclusion: Inherent depressive FH/Wjd rats were more sensitive to neonatal colon acetate stimulation, presenting as visceral hypersensitivity which maybe associated with increased MC amounts and over-expression of 5-HT and IDO in colon, suggesting that depression disorder may aggravate functional disturbance of gastrointestinal tract by regulating the response to inflammatory stimulation.

Objective: To explore the analgesic effect and action mechanism of electroacupuncture (EA) on gastric ulcer rats with liver-depression syndrome., Methods: Through open-field experimental method, 45 qualified SPF-grade male SD rats were selected and divided into a blank group, a model group and an EA group according to random number table method, 15 rats in each group. The model of gastric ulcer rats with liver-depression syndrome was established in the model group and the EA group by using chronic unpredictable stimulation combined with acetic acid burning method. Rats in the blank group did not receive intervention. Rats in the model group were treated with fixation and immobilization for 13 days. Rats in the EA group were treated with EA at "Liangqiu" (ST 34) and "Ganshu" (BL 18); EA voltage was 2 V; disperse-dense wave was selected with 4 Hz of disperse wave and 15 Hz of dense wave, and the intensity of EA was according to the slight vibration of local skin and; muscles; the needles were retained for 20 min, once a day for consecutive 6 days; there was an interval of 1 day' and the treatment was given for 2 weeks. The general condition, open-field experimental result and gastric ulcer index were observed; the western blotting method was applied to measure the expression of vanilloid receptor subtype 1 (VR1) in hypothalamus and gastric antral mucosal, and ELISA method was applied to test the expression of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in hippocampus., Results: After model establishment, the general behavior condition in the model group was inferior to that in the blank group, which was obviously improved after EA. The range of motion in the model group was less than that in the blank group (P<0.01) while that in the EA group was higher than that in the model group (P<0.01). The ulcer inhibition rate was. 54.95%, and the ulcer index in the EA group was lower than that in the model group (P<0.01). Compared with; the blank group, the expression of VR1 in hypothalamus and gastric antral mucosal in the model group was increased (P<0.05); compared with the model group, the expression of VR1 in the EA group was reduced (P<0.05). Compared with the blank group, the expression of 5-HT an NE in hippocampus in the model group was significantly reduced (both P<0.01); compared with the model group, the expression of 5-HT and NE in the EA group was increased (both P<0.01)., Conclusion: EA at "Liangqiu" (ST 34) and "Ganshu" (BL 18) has certain analgesic effect in gastric ulcer rats with liver-depression syndrome, which is likely to be related with lowering the contents of VR1 in hypothalamus and gastric antral mucosal and increasing the content of 5-HT and NE in hippocampus.

The present study is aimed to investigated the firing activity of pyramidal neurons and interneurons in the medial prefrontal cortex (mPFC) in rats with bilateral intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) by using in vivo extracellular recording. The results showed that the injection of 5,7-DHT reduced the 5-hydroxytryptamine (5-HT) levels in the mPFC and dorsal raphe nucleus in the rats. The firing rate of mPFC pyramidal neurons in rats with 5,7-DHT injection was significantly higher than that of normal rats, and the firing pattern of these neurons also changed significantly towards a more burst-firing, while the injection decreased the firing rate of mPFC interneurons and changed the firing pattern of the interneurons towards a more irregular. These results indicate that the lesions of the serotonergic neurons lead to the changes in the firing activity of mPFC pyramidal neurons and interneurons, suggesting that serotonergic system plays an important role in the regulation of the neuronal activity in the mPFC.

Objective: To evaluate the effect mechanism of warm acupuncture combined with auricular point sticking therapy and its efficacy on insomnia by monitoring the level of brain neurotransmitters in the insomnia patients., Methods: One hundred and thirty patients with insomnia were randomized into an observation group and a control group, 65 cases in each one. In the observation group, based on the treating principle of warming yang and benefiting qi, acupuncture was applied to Xinshu (BL 15), Pishu (BL 20), Shenshu (BL 23), Yaoyangguan (GV 3), Baihui (GV 20), Neiguan (PC 6) and Shenmen (HT 7). Warm acupuncture was supplemented at Xinshu (BL 15), Pishu (BL 20), Shenshu (BL 23) and Yaoyangguan (GV 3). The treatment was given once every day. In the control group, estazolam tablets, 0. 5 to 1 mg were prescribed for oral administration, 30 min before sleep at night. The treatment of 14 days was taken as one session and 2 sessions were required in the two groups. The encephal of luctuograph technology was used to observe the sleep quality and brain neurotransmitters before and after treatment in the two groups and the efficacy was compared between the two groups., Results: The total effective rate was 83.1% (54/65) in the observation group and 87.7% (57/65) in the control group. The efficacy was similar between the two groups (P > 0.05). In the observation group, after treatment, 5-HT and GABA/Glu were all increased compared with those before treatment (P < 0.05, P < 0.01) and norepinephrine (NE) was reduced compared with that before treatment (P < 0.05). The level of each index did not change significantly before and after treatment in the control group (all P > 0.05). The regulations of 5-HT, GABA/Glu in the observation group were superior to those in the control group (all P < 0.05)., Conclusion: The combined therapy of warm acupuncture and auricular point sticking method for warming yang and benefiting qi effectively improves brain neurotransmitters and essentially improves sleep quality of the patients with insomnia differentiated as yang deficiency pattern.

Objective: To study the mechanism of warm-hot nature Chinese drugs (WHNCD) for promoting blood circulation and removing blood stasis (PBCRBS) for intervening model rats of cold coagulation and blood stasis syndrome (CCBSS)., Methods: CCBSS rat model was set up in outbred SD rats using ice water immersion method. Totally 300 successfully modeled CCBSS rats were randomly divided into 5 groups according to the principle of balance weight, 60 in each group. Contents of triothyrone (T3), tetraiodothyroine (T4), progesterone (P), 5-hydroxytryptamine (5-HT), and noradrenalin (NE) were paralleledly detected in all groups. Then rats in each group were subdivided into 6 subgroups as the model group, the curcuma group, the Ligsticum Chuanxiong group, the safflower group, the Rhizoma Corydalis group, and the Olibanumg group. Besides, 5 normal control groups were set up for 5 indices, 50 rats in total. We need 70 rats (7 groups) to finish observing 1 index, 350 rats in total for 5 indices. Except those in the model group and the normal control group, rats were administered with corresponding decoction at 20 g crude drugs/kg body weight by gastrogavage, 3 mL each time, once daily for 7 successive days. Equal volume of normal saline was given to rats in the normal control group and the model group. Contents of T3, T4, P, 5-HT, and NE were detected before treatment and 1 week after treatment., Results: Compared with before treatment in the same group, T3 increased in the Ligsticum Chuanxiong group and the Olibanumg group, 5-HT increased in the Ligsticum Chuanxiong group, T4, NE, and P increased in all medicated groups (P < 0.05). Compared with the normal control group, contents of T3, T4, 5-HT, NE, and P in the model group decreased (P < 0.05). Compared with the model group, contents of T3, T4, 5-HT, and NE increased in each medicated group (P < 0.05). There was statistical difference in contents of P between the Ligsticum Chuanxiong group and the Olibanumg group (P < 0.05)., Conclusions: WHNCD for PBCRBS had regulatory roles in serum contents of T3, T4, P, and NE in modeled rats of CCBSS. They could promote the thyroid gland-gonadal axis function, enhance the function of the endocrine system, which might be one of the pharmacodynamic mechanism of WHNCD for PBCRBS in intervening CCBSS.

Objective: To observe the change of postoperative fatigue in rats after the effect of branched chain amino acid(BCAA) and associated antagonists on central neurotransmitter 5-HT metabolic pathway, and to investigate the role of 5-HT in the development of postoperative fatigue syndrome(POFS)., Methods: Fifty SD rats were randomly divided into sham operation group(C group, n=10), model group(M group, n=10), L-type amino acid transporter inhibitor group(L group, n=10), 5-HT uptake inhibitor group(F group, n=10) and branched chain amino acids(B group, n=10). The rats in the C group and the M group were injected with normal saline, while other three groups were respectively injected with BCH, fluoxetine, BCAA(val:leucine:isoleucine=5:3:2), on preoperative 1 h, postoperative day 1, 2, 3, 4. The rats, except for those in the C group, underwent resection of 70% of the middle small intestine with end-to-end anastomosis. General status of the rats was observed before and after surgery. Morris water maze test, including the hidden platform test and search space test (detecting the learning ability of rats) and tail suspension test (detecting physical endurance of rats) were used to evaluate the degree of POFS from postoperative day 1 to day 7. Concentration of tryptophan(TRP), 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) in different position of brain(hippocampus, striatum, hypothalamus) of rats were measured by high performance liquid chromatography(HPLC) at postoperative day 8., Results: As compared to the M group, other four groups showed better general condition and less fatigue. In the hidden platform test, M group showed the least time of crossing platform as compared to other four groups(all P<0.05). Meanwhile, M group and B group performed the longer incubation period than C group and L group(all P<0.05). In search space test, M group and B group showed less time of crossing platform, but there were no significant differences among the groups(all P>0.05). In tail suspension test, M group and F group showed lower score of physical strength than L group and B group(all P<0.05). Levels of TRP in the L, F, B groups were lower compared to the M group(all P<0.01) in brain tissue. The least concentration of striatum 5-HT was found in the C group but there were no significant differences among the M, L, F and B groups. Level of 5-HIAA in the M group, only in hypothalamus, was higher than that in the F group(P<0.05), but no significant differences between the M group and the L and B groups were found., Conclusion: BCAA and associated antagonists (BCH, fluoxetine) can improve POFS by reducing the absorption of TRP that results in decreased synthesis of central 5-HT.

Objective: To observe the effect of manual acupuncture stimulation on changes of hippocampal monoamine neurotransmitter levels and expression of 5-hydorxytryptamine (5-HT) mRNA, dopamine (DA) mRNA and acetylcholine esterase (AChE) mRNA in methamphetamine addiction rats, so as to explore its mechanism underlying improvement of drug addiction., Methods: SD rats were randomly divided into normal control, model and manual acupuncture groups (n=10 in each group). Drug addiction model was established by i.p. of methamphetamine (5 mg/kg), once a day for 15 days. Manual acupuncture stimu- lation was applied to "Baihui" (GV 20) and "Dazhui" (GV 14) once daily for 10 days. The contents of hippocampal 5-HT, DA, acetylcholine (ACh), AChE were measured by ELISA. The expressive Ilieels of hippocampal 5-HT mRNA, DA mRNA and AChE mRNA were determined by fluorescence quantitative RT-POR., Results: In comparison with the normal control group, the con- tents of 5-HT, DA, ACh and AChE and the expression levels of 5-HT mRNA, DA mRNA and AChE mRNA were significantly increased in the model group (P<0.01, P<0.05). After acupuncture intervention, the levels of the above-mentioned 7 indexes were uniformly and significantly down-regulated in the manual acupuncture group (P<0.01, P<0.05)., Conclusion: Manual acupuncture stimulation of GV 20 and GV 14 can adjust methamphetamine addiction-induced changes of some hippocampal monoa- mine neurotransmitters and expression levels of 5-HT, DA and AChE genes.

This study is to investigate the sedative and hypnotic effects of a novel compound H1208. The sedative activity of H1208 was investigated by recording the spontaneous locomotor activity of mice. The hypnotic property was evaluated by the latency and duration of sleep (loss of righting reflex) in mice and the effect of hypnotics on sleep pattern of electroencephalogram were studied in conscious, freely moving mice with chronically implanted electrodes. The brain monoamine neurotransmitters levels in mice were measured by high performance liquid chromatography-electrochemical detection. The spontaneous locomotor activity was decreased by 56.7% and 80.2% in H1208 (5 and 25 mg x kg(-1), ip) treated mice, respectively. The loss of righting reflex was directly induced in mice after H1208 (60 mg x kg(-1), ip) administration. The non-rapid eye movement sleep increased significantly by 131% and 259%, respectively, within 3 hours after H1208 (30 and 60 mg x kg(-1), ip) administration. However, the rapid eye movement sleep decreased significantly. The contents of DA in the striatum and cortex and 5-HT in the cortex decreased significantly. These results demonstrated that H1208 has potent sedative and hypnotic effects, which may be closely related to the decreased contents of DA and 5-HT in mouse brain.

Objective: The changes of pain threshold and expression of 5-hydroxytryptamine(5-HT) and c-Fos in spinal dorsal horn of rats were observed after targetedly damaged the cerebraspinal fluid-contacting nucleus (CSF-contacting nucleus) to provide experimental evidence for the mechanism of regulating pain CSF-contacting nucleus involved in., Methods: Male adult SD rats were divided into control, sham, choleratoxin subunit B conjugated with horse-radish peroxidase (CB-HRP)and damage groups randomly. The pain threshold using mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were recorded and analyzed. Immunofluorescence method was used to observe the expression of 5-HT and c-Fos in spinal dorsal horn., Results: Compared with the control, sham and CB-HRP groups, the MWT and TWL of the damage group were significantly increased (P < 0.05). The results of immunofluorescence showed that 5-HT was detected in neurons of CSF-contacting nucleus. In the damage group, the number of neurons of CSF-contacting nucleus reduced gradually, and no survived neurons were observed at the 10th day. Meanwhile, both the expression of 5-HT and c-Fos in spinal dorsal horn increased gradually, and negatively correlated with the change of pain threshold., Conclusion: The method of targeted damaging CSF-contacting nucleus by cholera toxin subnit B conjugated with saporin(CB-SAP) is scientific and reliable, and it results in the changes of pain threshold and expression of 5-HT and c-Fos in spinal dorsal horn of rats. This study suggests that CSF-contacting nucleus participate in the regulation of pain, moreover, 5-HT and c-Fos play important roles in this regulation.

Objective: To observe the effect of electroacupuncture (EA) stimulation of "Ganshu" (BL18) on expression of substance P (SP) in the gastric mucosa and hypothalamus tissues and hippocampal 5-hydroxytryptamine (5-HT) content in rats with depression + gastric ulcer, so as to explore its mechanism underlying improvement of depressive gastric ulcer., Methods: A total of 60 SD rats were equally randomized into normal, model, EA-BL18 and non-acupoint groups. The depression + gastric ulcer model was established by chronic unpredictable mild stress (CUMS) paradigm for 21 days in accordance with Willner and colleagues' methods (1987), and injection of 90% glacial acetic acid (0.01 mL) into the sub-serous layer near the gastric antrum under anesthesia on day 10 after starting CUMS. Following modeling, EA (4 Hz/15 Hz, 2 V) was applied to bilateral "Ganshu" (BL 18) for 20 min, once daily for 2 weeks, with one day's interval between two weeks. The non-acupoint was located about 2.5 cm lateral to the umbilicus and stimulated by EA similar to EA-BL18. The rats' locomotor ability was assessed by open field tests (crossing and rearing numbers). The gastric ulcer index was calculated according to Guth's method, and hypothalamic and gastric antrum SP immunoactivity was determined by immunohistochemistry and hippocampal 5-HT content was detected by ELISA., Results: After modeling, compared to the normal group, both crossing number and rearing number of open field tests on day 21 and 34 were significantly decreased in the model group (P < 0.01), while compared to the model group, both crossing and rearing numbers on day 34 were considerably increased in the EA-BL18 group (P < 0.01) rather than in the non-acupoint group (P > 0.05). Following modeling, the gastric ulcer index, SP expression levels in the gastric antrum and hypothalamus tissue were obviously increased in the model group (P < 0.01), and notably decreased in the EA-BL18 group (P < 0.01) but not in the non-acupoint group (P > 0.05). The hippocampal 5-HT content was remarkably lower in the model group than in the normal group, but obviously higher in the EA-BL18 group than in the model group (P < 0.01). No significant difference was found between the model and non-acupoint groups in the hippocampal 5-HT content (P > 0.05)., Conclusion: EA of "Ganshu" (BL18) can promote locomotor and reduce gastric ulcer index in depression + gastric ulcer rats, which may be related to its effects in lowering gastric and hypothalamic SP immunoactivity and in raising hippocampal 5-HT content.

In view of the effective traditional Chinese medicine (TCM) in the treatment of clinical depression, the mechanism is not clear, this study attempts to research the cause of depression in a complex situation to lay the foundation for the next step of TCM curative effect evaluation. Based on the brain wave of 120 depression patients and 40 ordinary person, the change regulation of acetylcholine, dopamine, norepinephrine, depression neurotransmitters and excited neurotransmitters in the whole and various encephalic regions' multi-neurotransmitters of depression patients-serotonin are analysed by search of encephalo-telex (SET) system, which lays the foundation for the diagnosis of depression. The result showed that: contrased with the normal person group, the mean value of the six neurotransmitters in depression patients group are: (1) in the whole encephalic region of depression patients group the dopamine fall (P < 0.05), and in the double centralregions, right temporal region and right parietal region distinct fall (P < 0.01); (2) in the right temporal region of depression patients group the serotonin rise (P < 0.05); (3) in the right central region, left parietal region of depression patients group the acetylcholine fall (P < 0.05), left rear temporal region fall obviously (P < 0.01). The correlation research between antagonizing pairs of neurotransmitters and neurotransmitters: (1) the three antagonizing pairs of neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression neurotransmitters and excited neurotransmitters, in ordinary person group and depression patients group are characterizeed by middle or strong negative correlation. Serotonin and dopamine, which are characterized by weak negative correlation in the right rear temporal region of ordinary person group, are characterized by strong negative correlation in the other encephalic regions and the whole encephalic (ordinary person group except the right rear temporal region: the range of [r] is [0.82, 0.92], P < 0.01)/(depression patients group:the range of [r] is [0.88, 0.94], P < 0.01); acetylcholine and norepinephrine, in the whole and various encephalic region are characterized by middle negative correlation(ordinary person group:the range of [r] is [0.39, 0.76], P < 0.01 or P < 0.05)/(depression patients group: the range of [Ir] is [0.56, 0.64], P < 0.01); depression neurotransmitters and excited neurotransmitters are characterized by middle strong negative correlation (ordinary person group: the range of [r] is [0.57, 0.80], P < 0.01)/(depression patients group: the range of [r] is [0.68, 0.78], P < 0.01). (2) The two neurotransmitters which are not antagonizing pairs of neurotransmitters, serotonin and excited neurotransmitters, or acetylcholine and depression neurotra-nsmitters, or dopamine and depression neurotransmitters in the various encephalic regions are characterized by weak negative correlation. Serotonin and excited neurotransmitters are characterizeed by weak negative correlation (ordinary person group: in the right central region, left parietal region, double front temporal regions, right rear temporal region, the range of [r] is [0.25, 0.50], P < 0.01 or P < 0.05)/(depression patients group: in the whole encephalic regions, double parietal regions, double occipital regions, right front temporal region, left central region, left frontal region, the range of [r] is [0.18, 0.37], P < 0.01 or P < 0.05); acetylcholine and depression, neurotransmitters are characterized by weak negative correlation (ordinary person group: in the double frontal regions, left parietal region, left front temporal region, right rear temporal region, the range of [r] is [0.31, 0.46], P < 0.01 or P < 0.05)/(depression patients group: in double rear temporal regions, right front temporal region, double occipital regions, left central region, the range of [r] is [0.20, 0.32] , P < 0.01 or P < 0.05); do-pamine and depression neurotransmitters are characterized by weak middle negative correlation (ordinary person group: in left parietal region, right central region, left frontal region, left occipital region, double front temporal regions, the range of [r] is [0.33, 0.68], P < 0.01 or P < 0.05)/(depression patients group: in the whole region and other various regions except the left frontal region, right central region, the range of Irl is [0.21, 0.34], P < 0.01 or P < 0.05). Dopamine and acetylcholine or norepinephrine and serotonin are characterized by weak positive correlation in all encephalic regions. Dopamine and acetylcholine are characterized by weak positive correlation (ordinary person group: in left frontal region, right parietal region, left front temporal region and left rear temporal region, the range of [r] is [0.37, 0.46], P < 0.01)/(depression patients group: in the whole region and the orther various regions except the double central regions, the range of [r] is [0.23, 0.5], P < 0.01 or P < 0.05); norepinephrine and serotonin are characterized by weak positive correlation (ordinary person group: in double front temporal regions, double rear temporal regions, right frontal region and left parietal region, the range of [r] is [0.34, 0.48], P < 0.01 or P < 0.05)/(depression patients group: in the whole and various regions, the range of [r] is [0.18, 0.42], P < 0.01). The main differences between the depression patients group and ordinary person group are: (1) In the whole regin, left frontal region and right central region of depression patients group, the six neurotransmitters all fall normally (P < 0.05). (2) The percent of dopamine falling or including dopamine falling, or including dopamine falling and serotonin rising in depression patients group increases. The percent of dopamine falling or including dopamine falling in the whole region, right frontal region, right central region increases (P < 0.01), such as dopamine decreasing, serotonin increasing dopamine decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing, dopamine decreasing norepinephrine increasing depression neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on. (3) The percent of acetylcholine falling, or including acetylcholine falling, or including acetylcholine falling and neurotransmitters (beta)-receptor)rising in depression patients group increases. The percent of acetylcholine falling, or including acetylcholine falling in the right temporal region, double central regions increases (P < 0.05 or P < 0.01), such as acetylcholine decreasing, acetylcholine decreasing neurotransmitters increaseng, acetylcholine decreasing neurotransmitters increasing depression neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on. It's showed in research that depression patients' brain are characterized by multi-neurotransmitters abnormal, the synchronous change of multi-neurotransmitters has some certain regularities, which are not the simple linear relation. It's conformed that the three antagonizing pairs, neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression eurotransmitters and excited neurotransmitters of ordinary person group and depression patients group, are both characterized by strong antagonizing relation, that the two neurotransmitters which are not antagonizing pairs of neurotransmitters are characterized by weak positive correlation or negative correlation, prompt maybe has the indirect causal relationship. And the change of six neurotransmitters in depression patients' various encephalic regions is rather complex. It's conformed preliminarily that the right frontal region and right central region are characterized by dopamine decreasing, acetylcholine decreasing, serotonin increasing dopamine decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing, dopamine decreasing norepinephrine increasing excited neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing, acetylchoine decreasing neurotransmitters increasing, acetylcholine decreasing neurotransmitters increasing excited neurotransmitters decreasing and so on. Contrasted with the ordinary person group, the depression patients group have the notable difference.

Objective: To observe the effects of electroacupuncture (EA) stimulation of "Neiguan"(PC 6) and "Shenmen" (HT 7) on 5-hydroxytryptamine (5-HT) levels in the paraventricular nucleus (PVN) region of hypothalamus and serum in hyperlipidemia rats with acute myocardial infarction (AMI)., Methods: A total of 80 SD rats with hyperlipidemia were used in the present study. Among them, 20 rats were randomly selected to be the sham-operation group, and the rest 60 cases were used to make the AMI model by occlusion of the anterior descending branch of the left coronary artery. The 60 rats who were identified to be successful in AMI were randomly divided into model group, EA-PC 6 group and EA-HT 7 group (20 rats/group). EA (2 Hz, 2 mA) was applied to bilateral PC 6 and HT 7 for 20 min, once daily for 5 days. The contents of 5-HT of hypothalamic PVN region and serum were examined by enzyme linked immunosorbent assay (ELISA) and radioimmunoassay, respectively., Results: Following AMI, marked myocardial injury (swelling, breakage, disappearance of local transverse striations and necrosis of myocytes) with infiltration of neutrophil granulocytes was found in the model group, while in both EA-PC 6 group and EA-HT 7 group, moderate swelling (no breakage) of fewer myocardial fibers with mild infiltration of neutrophil granulocytes was found, indicating a marked improvement of myocardial injury after EA treatment. Compared with the sham-operation group, the content of 5-HT was obviously decreased in the hypothalamic PVN region and significantly increased in serum in the model group (P < 0.01). After EA intervention, the content of 5-HT was considerably up-regulated in the hypothalamic PVN region and apparently down-regulated in serum in both EA-PC 6 and EA-HT 7 groups in comparison with the model group (P < 0.01). No significant differences were found between EA-PC 6 and EA-HT 7 groups in regulating hypothalamic and serum 5-HT levels (P > 0.05)., Conclusion: EA stimulation of both PC 6 and HT 7 can relieve acute ischemic injury of the myocardium in hyperlipidemia rats, which is probably partially related to its effect in promoting the release of 5-HT from the hypothalamic PVN region.

This study is to explore the amelioration of piperine on chronic acute combining stress rat with depression-like behavior, visceral sensitivity, and its effect on the expression of serotonin (5-HT) and synaptophysin. Forty two SD rats were divided into seven groups: blank group, model group, piperine (12.5, 25, 50 and 100 mgkg-1, ig) and imipramine (10 mgkg-1, ip) groups. The rat model of irritable bowel syndrome was established by chronic acute combining stress, and then to evaluate depression-like behavior and visceral sensitivity. The expressions of 5-HT and synaptophysin in the hippocampus and colon were determined by high performance liquid chromatography (HPLC) and Western blotting, respectively. The duration of immobility of IBS rat in the forced swimming test had been significantly increased, the sucrose consumption of IBS rat had been reduced and visceral sensitivity was obviously elevated in the IBS model group as compared with those in the normal control group (P<0.05, P<0.01). As compared with those in the normal control group, the expression of 5-HT significantly decreased, 5-HIAA/5-HT ratio significantly increased in the hippocampus of IBS model group (P<0.05), but opposite presentations were noted in the colon (P<0.05). As compared with that in the normal control group, the synaptophysin expression in the hippocampus decreased significantly but obviously increased in the colon (P<0.05). Piperine improved the behavior of IBS rats, and reversed the levels of 5-HT and 5-HIAA, and 5-HIAA/5-HT proportion in the hippocampus and colon (P<0.05); besides, they significantly reverse the synaptophysin level in the hippocampus and colon (P<0.05). The presence of depression and visceral sensitivity had been changed in IBS rats, with abnormal expression of 5-HT and synaptophysin in the brain-gut system. Piperine can ameliorate the changes of the behavior and regulation of serotonin and synaptophysin expression in IBS rat model.

Objective: To observe antidepressant effects of Kuanxinjieyutang (KXJYT), short-term aerobic exercise and their joint intervention and its possible mechanism., Methods: Ninty-six SPF male KM mice were randomly divided into control group, imipramine, low dose (KXJYT 1.8 g crude drugs/kg bw/time/day), high dose (3.6 g crude drugs/kg bw/time/day), exercise group (swimming 30 min/times/day), joint group (low dose and swimming ), with 8 days intervention. The antidepressant effect was evaluated by forced swimming, tail suspension test and overhead cross maze test. After mice were killed, brain monoamine neurotransmitter levels of mice were detected by ELISA, and BDNF expression in brain was analyzed by Western blotting., Results: High dose group showed antidepressant effect like imipramine while low dose didn't. Exercise group showed similar or better antidepressant effect than imipramine. Joint group showed better interaction antidepressant effect. Brain NE, DA of high dose group and brain NE, DA and 5-HT content of exercise group increased significantly, similar to imipramine. Brain NE,DA and 5-HT content of Joint group were significantly higher than those of imipramine. The protein expression of BDNF in brain was more in imipramine, high dose,exercise and joint groups than that of control group, sports group was higher than that of low dose and high dose group, joint group was obviously higher than other groups., Conclusion: Moderate KXJYT, short-term aerobic exercise and their joint intervention have obvious antidepressant effect on mild depression. Its mechanism may be related to increasing brain NE and 5-HT content, and inducing brain BDNF expression, which may affect the nerve regeneration and plasticity, improve cognitive function.

Objective: To observe effects of xuefu zhuyu Oral Liquid (XZOL) on the brain behavior and monoamine neurotransmitter 5-HT, and brain derived neurotrophic factor (BDNF) content on depression model rats., Methods: Male SD rats were randomly divided into the control group, the model group, the XZOL group, and the Deanxit Tablet group, 12 in each group. The depressive rat model was established by chronic unpredictable mild stress method. XZOL was administered to rats in the XZOL group by gastro-gavage, while Deanxit Tablet was given to those in the Deanxit Tablet group by gastrogavage. The intervention lasted for two weeks. The behavioral changes were observed by sucrose water consumption test and open-field test. The 5-HT and BDNF contents were detected using ELISA., Results: After chronic stress stimulus, experimental rats in the model group might have abnormal behavioral changes and lowered 5-HT content, showing statistical difference when compared with the control group (P <0.01). No obvious change in stimulated rats' behavior after intervention of XZOL and Deanxit Tablet. 5-HT content was not obviously reduced (P>0.05). Besides, XZOL was superior to Deanxit Tablet in increasing the 5-HT content (P<0.05). But the brain BDNF level of rats in the model group was not statistically different from that of rats in the model group (P >0.05), while the brain BDNF level of rats in the XZOL group and the Deanxit Tablet group was lower than that of rats in the model group (P <0.01)., Conclusions: Stress can lead to behavioral changes and lowered 5-HT content of rats. The intervention of XZOL could fight against depression-induced behavioral changes and increase 5-HT content. But it did not significantly affect the brain BDNF level. We inferred that it might not effect through the BDNF pathway.

This study is to offer a clinical pain-depression dyad therapy of ferulic acid, the pain-depression dyad induced by reserpine was established and the dose-effect relationship of ferulic acid on ameliorating pain-depression dyad was explored. Mice were randomly divided into control group, reserpine + vechile and reserpine + ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)) groups. The reserpine treated mice were tested with thermal hyperalgesia, mechanicial allodynia and forced swimming tests, and the SOD and NO levels of hippocampus and frontal cortex were measured. Moreover, the HPLC-ECD was used to detect the changes of central monoamines concentrations. Compared with control group, reserpine can induce a significant decrease in the nociceptive threshold and increase in the immobility time of the forced swimming test. The results suggested that reserpine significantly increased the level of nitrite in hippocampus and frontal cortex and reduced the levels of SOD, 5-HT and NE in these two brain regions. However, these indexes can be a dose-dependently reversed by ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)). Ferulic acid can reverse pain-depression dyad, especially at the dose of 80 mg x kg(-1). In addition, it can influence oxidative stress and monoamine level.

Objective: To observe the changes of thoracic duct lymph volume and the contents of histamine (HA), 5-hydroxytryptamine (5-HT), etc. in the lymph after acupuncture or thermal acupuncture interventions, in order to investigate the effect of lymphatic system in transmitting acupuncture and moxibustion signals., Methods: A total of 45 male Wistar rats were randomly divided into control group, acupuncture group, and thermal acupuncture (acupuncture with the needle warmed by burning moxa) group (n = 15/group). The rat thoracic duct lymphatic fistula model was replicated. Acupuncture or thermal acupuncture was applied to "Zusanli" (ST 36), and the changes of thoracic duct lymph volume and the concentrations of HA, 5-HT in the lymph were observed., Results: Compared with the control group, the thoracic duct lymph volume in acupuncture group and thermal acupuncture group were obviously increased (P < 0.05), while the concentrations of lymph HA and 5-HT in both acupuncture and thermal acupuncture groups had no significant changes (P > 0.05)., Conclusion: Both acupuncture and thermal acupuncture interventions can increase the thoracic duct lymph volume, but have no effects on lymph HA and 5-HT contents in normal rats.

As for an important central regulatory neurotransmitter involving acupuncture effect, serotonin (5-HT) is worthy of being paid with more attention. In the present paper, the authors review development of researches on the involvement of 5-HT and its receptor subunits in pain perception, acupuncture analgesia, and other effects of acupuncture (anti-depression, weight-reduction, etc.). Many studies showed that acupuncture intervention could modulate the content and activity of central 5-HT, and these changes varied under different conditions. Hence, the relationship between 5-HT and other neurotransmitters in acupuncture analgesia and its different functions in different regions of the central nervous system should be considered comprehensively.

Objective: To investigate the relationship between serotonin (5-HT) and epilepsy and the mechanism of learning-memory in pilocarpine (PILO)-induced epileptic rats after 5,7-dihydroxytryptamine (5,7-DHT) microinjection in median raphe nucleus., Methods: Adult S D rats were randomly divided into 3 groups: PILO group, PILO+ 5,7-DHT group, vehicle control group; PILO group was divided into two groups by status epilepticus (SE): PILO + SE group and PILO - SE group. The rats' seizures and cortex electroencephalography (EEG) were observed by video EEG. The rats' spatial learning-memory was evaluated by Morris water maze. Finally, serotonergic neuron in raphe nuclei was observed by immunohistochemistry., Results: After treatment of 5,7-DHT (PILO + 5,7-DHT group), the success rate, the mortality and the frequency of chronic spontaneous seizures in pilocarpine-induced epilepsy model were all improved. Compared with the control group, the number of serotonergic neuron in raphe nuclei was decrease in PILO + SE group (P < 0.05). Moreover, it's extremely decrease in PILO + 5,7-DHT group (P < 0.01). Compared with control group, the mean escape latency was prolonged, the times of crossing target was decreased and the retention time in target zone was shortened in PILO + SE group (P < 0.05), but there was no significant difference between PILO + SE group and PILO + 5,7-DHT group., Conclusion: Depletion of serotonin may facility the rats' epileptic seizures, but we could not interpret which may cause epileptic rats' cognitive deficit.

Objective: To study the effects of ketamine and alcohol on learning and memory in mice and its possible mechanism., Methods: Forty mice were divided into 4 groups: normal control group, ketamine group, alcohol group, and alcohol plus ketamine group. Ketamine and alcohol were given by intraperitoneal injection and intragastric administration, respectively, 1 time per day, for 14 days. The ability of learning and memory in mice was tested by the method of step-down and Morris water maze. Acetylcholine (ACh) and 5-hydroxy tryptamine(5-HT) in mice brain tissue were analyzed for the possible mechanism., Results: (1) Step-down: The treatment groups lessened the latency and added wrong times (P < 0.05). The number of errors in the combined treatment group significantly increased comparing with the single drug treatment group (P < 0.05). (2) Morris water-maze: The treatment groups prolonged the latency (P < 0.05), reduced the target quadrant activity time significantly (P < 0.05), and decreased the numbers of crossing the former platform significantly (P < 0.05). (3) Biochemical index determination: The concentrations of ACh and 5-HT in treatment groups decreased significantly (P < 0.05), showed a more decreasement comparing with the single drug treatment group., Conclusion: Ketamine has a synergistic effect with alcohol on learning and memory impairment in mice, which may be related to the common inhibitive effect on the ACh and 5-HT.

Objective: To observe anti-fatigue effect and mechanisms of pre-electroacupuncture (EA) at "Zusanli" (ST 36) in rats undergoing acute treadmill running., Methods: Fifty male SD rats were randomly divided into three groups: a quiet group (group Q, n = 10), a model group (group M, n = 20) and an EA preconditioning group (group EAP, n = 20). After adaptation for undergoing treadmill running, all the rats in group M and group EAP were trained on acute treadmill running. Besides, EA with continuous waves, 2 Hz in frequency and 2 mA in intensity was applied at bilateral "Zusanli" (ST 36) for 30 min, which was applied once daily for continuous 6 days before treadmill running for the rats in Group EAP. Plasma lactate contents were measured immediately and 3 hours after treadmill running, respectively. Changes of dopamine (DA) and serotonin (5-HT) contents obtained immediately and 3 hours after treadmill running, respectively, in hypothalamus and striatum, were detected and compared, and DA/5-HT ratios were calculated., Results: Compared with group Q, the levels of blood lactate and hypothalamic 5-HT tented to increase in rats of group M, and the contents of hypothalamic DA increased significantly (P < 0.01), while the contents of striatal DA and 5-HT in group M decreased significantly (both P < 0.01) at 3 h after treadmill running. Immediately after treadmill running, the contents of DA and 5-HT increased significantly in hypothalamus (both P < 0.01), but decreased significantly in striatum (both P < 0.01) in group EAP, compared with those in group M. Moreover, EA pretreatment markedly decreased the levels of blood lactate (P < 0.05) and hypothalamic 5-HT (P < 0.01), and obviously elevated the ratio of DA/5-HT in the hypothalamus (P < 0.01) at 3 h after treadmill running., Conclusion: Preventive EA at "Zusanli" (ST 36) can accelerate recovery from fatigue, which may be related to its reducing accumulation of blood lactate, elevating DA/ 5-HT ratio in the hypothalamus of the rats undergoing treadmill running.

Despite substantial advancement in psychopharmacological and electro-magnetic treatments over the last decades on the depression patients, there are non-responders remain with a chronic disease and high suicidal risk yet. Deep brain stimulation (DBS) is now being experimentally to treat the intractable depression and yielded an impressive therapeutic benefit, and especially few adverse effect occurred. The beneficial action of DBS is closely related to the stimulation sit. And the efficacy of high frequency stimulation of lateral habenula is one of the best choice. In depression, the concentration of 5-HT released by the raphe nuclei is decreased. It's due to mainly the overactivation of the lateral habenula. High frequency stimulation of lateral habenula impairs the activation of lateral habenula, and the inhibitory effect of lateral habenula on raphe nuclei is decreased. Then, the 5-HT concentration released by the raphe nuclei is increased, the pathological changes of depression is eliminated. The lateral habenula could be a promising novel target for BDS in the cases of intractable depression.