慢性应激抑郁模型大鼠脑内5HT_(1A)和5-HT_(2A)受体的变化

为了在 5 羟色胺受体水平研究抑郁症的机制和三环类抗抑郁药物 (TCAs)阿米替林的药理学机理 ,将 2 4只SD雄性大鼠随机均分为三组 ,即对照组、抑郁组、阿米替林治疗组。应用 [3H]8 OH DPAT、[3H]Ketanserin作为标记配基 ,采用放射性配体受体结合法 ,分别测定大鼠海马 5 HT1A受体、大脑皮层 5 HT2A 受体结合。结果显示 :抑郁大鼠海马 [3H]8 OH DPAT特异性结合 (1 8 78± 5 6 2fmol mgprot) ,较正常对照组 (2 6 1 2± 5 5 2fmol mgprot )明显下降(P <0 0 5 )。抑郁大鼠大脑皮层 [3H]Ketanserin特异性结合 (1 1 2 5 8± 4 2 1fmol mgprot) ,较正常对照组 (86 2 8±4 2 4fmol mgprot)明显增加 (P <0 0 5 )。阿米替林治疗 3周后 ,可使抑郁大鼠海马 5 HT1A 受体与大脑皮层 5 HT2A 受体结合恢复正常。提示 :海马 5 HT1A受体结合下降、大脑皮层 5 HT2A 受体结合增加可能与抑郁症病因有关 ;海马 5 HT1A 受体、大脑皮层 5 HT2A 受体是阿米替林发挥抗抑郁作用的环节。

我院5HT_3受体拮抗剂应用分析

目的:为了解本院5-HT_3受体拮抗剂使用情况,促进此类药物的合理应用。方法:采用回顾性分析方法,对2015年1月份各临床科室使用昂丹司琼、阿扎司琼、雷莫司琼和托烷司琼4种5-HT_3受体拮抗剂药物的住院患者用药的合理性进行分析评价。结果:5-HT_3受体拮抗剂使用不合理情况较严重,除了血液科合理比例达到100%以外,其余科室合理比例均小于20%。结论:住院患者5-HT_3受体拮抗剂使用存在诸多问题,需进一步开展医嘱点评及合理性分析,规范5-HT_3受体拮抗剂的应用。

针刺捻转补泻手法对自发性高血压大鼠顶叶皮质NO、5HT的影响

目的观察针刺捻转补泻手法对自发性高血压大鼠(SHR)顶叶皮质一氧化氮(NO),5-羟色胺(5-HT)的影响,探讨捻转补泻手法对SHR血压调控的中枢作用机制,为捻转补泻效应差异提供客观依据。方法将40只SHR随机等分为模型组、针刺组、捻转补法组、捻转泻法组,每组各10只。WKY大鼠10只作为空白组对照。除空白组、模型组外,其余各组分别用不同的手法针刺"太冲穴";用无创血压仪测各组大鼠尾压,于针刺前1 d测量1次,针刺第3、8、13、18、23、27日测量。针刺28 d后取顶叶皮质,采用微板法与酶联免疫吸附试验(ELISA)测定其中NO,5-HT的含量,比较各组间指标有无差异。结果捻转泻法组血压明显降低,与模型组及其余各治疗组差异显著(P<0.05);与空白组比较,模型组顶叶皮质NO,5-HT含量明显降低,有显著差异(P<0.05);捻转泻法组顶叶皮质NO,5-HT含量较模型组、针刺组、捻转补法组明显升高,有显著差异(P<0.05),和空白组比较无统计学差异(P>0.05)。结论 SHR顶叶皮质中5-HT含量与NO含量的降低可能是其高血压形成的中枢机制之一,对"太冲穴"施以针刺捻转泻法可以使顶叶皮质中降低的5-HT、NO含量得到升高,有效降低血压水平,中枢5-HT、NO参与了针刺捻转手法对SHR的血压调节过程。

Possible association of the 5-HTTLPR serotonin transporter promoter gene polymorphism with premature ejaculation in a Turkish population

We evaluated the genotypes of the serotonin transporter gene （5-HTT） in patients with premature ejaculation （PE） to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene （5-HTTLPR） were determined. The 5-HTTLPR （serotonin transporter promoter gene） genotypes in PE patients vs. controls were distributed as follows： L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene： LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the Z-test. The short （S） allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls （P 〈 0.05）. We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup （such as primary and secondary PE） responses to selective serotonin reuptake inhibitors as well as ethnic differences.

Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress

Previous studies suggest that serotonin （5-HT） might interact with brain-derived neurotrophic factor （BDNF） during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

Heat-Killed <i>Lactobacillus brevis</i>SBC8803 Induces Serotonin Release from Intestinal Cells

Previously, we reported that changes induced in autonomic neurotransmission in rats by Lactobacillus brevis SBC8803 may be mediated by serotonin 3 (5-HT3) receptors. In this study, we evaluated the effects of heat-killed L. brevis SBC8803 on serotonin (5-HT) releasing from intestinal cells. In the in vitro study, L. brevis SBC8803 stimulated 5-HT release from cultured rat endocrine RIN-14B cells (SBC8803 vs. sterile water;P in vivo study, 2 mg of heat-killed L. brevis SBC8803 was administered using a stomach sonde (feeding needle) to C57BL/6J mice. Analysis of plasma by ELISA showed gradually increase in 5-HT concentrations (0 min vs. 60 min;P ex vivo cultured intestinal loops composed of duodenum and part of the jejunum, from C3H/HeN and C57BL/6J male mice indicated that L. brevis SBC8803 effectively induced 5-HT release (SBC8803 vs. sterile water;P L. brevis SBC8803 may stimulate 5-HT release from mouse intestinal cells such as enterochromaffin cells.

Differences of Plasma Levels of Tryptophan, Serotonin, 5-Hydroxyindole Acetic Acid, and Kynurenine between Healthy People and Patients of Major Monopolar Depression at Various Age and Gender

Background: It is not well analyzed whether there are differences in plasma levels of tryptophan (TRP) metabolites between healthy control people (HC) and patients of major monopolar depression (MMD). Methods: Ultra high-speed liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive patients. Results: There are no significant differences between plasma levels of TRP between HC and MMD. Plasma levels of TRP of HC are higher in young men, young women, old men, and old women in this order. Serotonin (5-HT) levels are higher in MMD than HC. Plasma levels of 5-HIAA of HC are also higher than those of patients of MMD. Plasma levels of kynurenine (KYN) of healthy old men and old women are higher than those of young men and old women. Plasma levels of KYN are higher in old women and young men of MMD than those of HC. Conclusion: Plasma levels of 5-HT are higher in patients of MMD than those of HC, which may suggest that use of drugs inhibiting the 5-HT transportation may increase plasma levels of 5-HT in MMD.

Serotonin controls axon and neuronal regeneration in the nervous system:lessons from regenerating animal models

Traumatic brain injury （TBI） is a mechanical injury to brain tissue that leads to an impairment of function and a broad spectrum of symptoms and disabilities; often, it is followed by diffuse axonal injury, which causes denaturation of the white matter and axon retraction, leaving patients with severe brain damage or even in a persistent vegetative state.

CLINICAL COMPARISON OF THE SELECTIVE SEROTONIN_3 ANTAGONISTS RAMOSETRON AND GRANISETRON IN TREATING ACUTE CHEMOTHERAPY-INDUCED EMESIS,NAUSEA AND ANOREXIA

Feng Fengyi , Zhang Pin , He Youjian 1, Li Yuhong1 , Zhou Meizhen2 , Chen Gang2 and Li Lin2 The Cancer Hospital of the CAMS & PUMC, Beijing 1000211 The Cancer Hospital of Sun Yat Sen University of Medical Sciences, Guangzhou 5100602Beijing Hospital of the Ministry of Health, Beijing 100730

Phenothiazine vs 5HT3 Antagonist Prophylactic Regimens to Prevent Post‐Anesthesia Care Unit Rescue Antiemetic: An Observational Study

Purpose: Our practitioners are asked to consider a patient’s postoperative nausea and vomiting (PONV) risk profile when developing their prophylactic antiemetic strategy. There is wide variation in employed strategies, and we have yet to determine the most effective PONV prophylactic regimen. The objective of this study is to compare prophylactic antiemetic regimens containing: phenothiazines to 5HT3 antagonists for effectiveness at reducing the incidence of Post‐Anesthesia Care Unit (PACU) rescue antiemetic administration. Methods: This is an observational study of 4392 nonsmoking, women who underwent general anesthesia for breast surgery from 1/1/2009 through 6/30/2012. Previous history of PONV or motion sickness (HxPONV/MS) and the use of PACU opioids were recorded. Prophylactic antiemetic therapy was left to the discretion of the anesthesia care team. We compared phenothiazines and 5HT3 antagonists alone and with a glucocorticoid to determine the most effective treatment regimen in our practice for the prevention of the administration of PACU rescue antiemetics. Results: Patients who received a phenothiazine regimen compared to a 5HT3 antagonist regimen were less likely to have an antiemetic administered in the PACU (p = 0.0100) and this significant difference in rates holds in a logistic regression model adjusted for HxPONV/MS and PACU Opioid use (p = 0.0103). Conclusions: Based on our findings our clinicians are encouraged to administer a combination of a phenothiazine and a glucocorticoid in female, nonsmoking surgical breast patients for the prevention of PACU rescue antiemetic administration.

Radiolabeling, docking studies, in silico ADME and biological evaluation of serotonin with 125I for 5-HTRs imaging

Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin receptors(5-HTRs), which is a promising tool in the determination of the receptor’s function and relationship with the diseases related to serotonin and its receptor dysfunction. Serotonin was effectively labeled via a direct electrophilic substitutional reaction using an oxidizing agent such as iodogen with 125I in a neutral medium, and 125I-serotonin was achieved with a maximum labeling yield of 91 ± 0.63% with in vitro stability up to 24 h. Molecular modeling was conducted to signify 125I-serotonin structure and confirm that the radiolabeling process did not affect serotonin binding ability to its receptors. Biodistribution studies show that the maximum gastro intestinal tract uptake of 125I-serotonin was 17.8 ± 0.93% ID/organ after 30 min postinjection and the tracer’s ability to pass the blood–brain barrier. Thus, 125I-serotonin is a promising single photon emission computed tomography tracer in the detection of 5 HTRs.

Serotonin enrichment of rice endosperm by metabolic engineering

In animals,serotonin is a neurotransmitter and mood regulator.In plants,serotonin functions in energy acquisition,tissue maintenance,delay of senescence,and response to biotic and abiotic stresses.In this study,we examined the effect of serotonin enrichment of rice endosperm on plant growth,endosperm development,and grain quality.To do so,TDCs and T5H were selected as targets for serotonin fortification.Overexpression of TDC1 or TDC3 increased serotonin accumulation relative to overexpression of T5H in rice grain.Transgenic lines of target genes driven by the Gt1 promoter showed better field performance than those driven by the Ubi promoter.Overexpression of T5H showed little effect on plant growth or grain physicochemical quality.In neuronal cell culture assays,serotonin induced neuroprotective action against apoptosis.Breeding of rice cultivars with high serotonin content may be beneficial for health and nutrition.

Effects of Activation and Blockade of Serotonin 5-HT1A Receptors on the Immune Response in Rats Selected for Different Levels of Aggressiveness

The present study examines the effects of serotonin (5-HT) 1A receptor ligands on humoral im-mune response in two rat lines selected for over 75 generations for the enhancement or elimination of aggression. Activation of presynaptic 5-HT1A receptors with a low dose of the selective 5-HT1A receptor agonist 8-OH-DPAT (0.1 mg/kg) or the blockade of postsynaptic 5-HT1A receptors with the antagonist WAY-100635 (1.0 mg/kg) did not affect the numbers of IgM-antibody forming cells (IgM-AFC) in the spleen of highly aggressive rats, which were characterized by higher immune responsiveness compared to nonaggressive line. On the other hand, the same doses of 8-OH-DPAT and WAY-100635, as well as a higher dose of 8-OH-DPAT (1.0 mg/kg), which is known to activate postsynaptic 5-HT1A receptors, produce immunostimulation in nonaggressive rats. However, only the highest dose of 8-OH-DPAT (5.0 mg/kg) was able to cause immunosuppression in nonaggressive rats that was mainly dependent on stimulation of postsynaptic 5-HT1A receptors. In contrast to nonaggressive rats, the dose of 1.0 mg/kg 8-OH-DPAT was sufficient to produce a decrease in the numbers of IgM-AFC in highly aggressive rats. Thus, pharmacological activation of pre- and postsynaptic 5-HT1A receptors, as well as the blockade of postsynaptic 5-HT1A receptors, produced different effects on the immune response in two lines of rats selected for high level of aggression or its absence. These data may have implications for more efficient treatments of a number of mental disorders associated with abnormal aggression.

Changes of Serotonin content and Turnover Rate in Hypothalamus of Female Rat during Fluorosis

The animal models of subacute and chronic fluorosis were devel-oped with injection of large doses of NaF (IP)and drinking water containing100 ppm F^- in female rats respectively. Serotonin content and turnover rate inhypothalamus of rat were determined with spectrofluorometry combined degra-dation blockade. 5-HT turnover rate in hypothalamus decreased during bothsubacute and chronic fluorosis. 5-HT content in hypothalamus increased duringsubacute fluorosis, but decreased during chronic fluorosis. These results suggestthat the influences on 5-HT metabolism of two kinds of fluorosis are not com-pletely identical. The decrease of 5-HT turnover rate in hypothalamus may be one of thepossible mechanisms of deficiency of pituitary prolactin and milk secretion dur-ing fluorosis.

THE APPLICATION OF SEROTONIN AND 5-HVDROXYINDOLE-3-ACETIC ACID IN THE DIAGNOSIS OF APUDOMA

In our report, the values of whole blood serotonin (5-HT) in 87 apudoma patients (diagnosed by operation and pathology) were summarized. Among them, the levels of urinary 5-hydroxyindole-3-acetic acid (5-HIAA) of 44 patients were also tested. The results showed that both parametres of apudoma patients were higher than those of non-apudoma, post-operative patients of apudoma as well as the normal. The increasing extent of the levels of whole blood 5-HT and urinary 5-HIAA in small intestinal carcihoid was the most obvious one but that of rectum was not. The referable diagnostic values suggested were: 5-HT>130 ng ml, 5-HIAA>30 mg/ 24 hours.

Extracellular Levels of 5HT and 5HIAA Increase after an Inflammatory Process in the Rat’s Insular Cortex

Serotonin (5HT) in the central nervous system has been associated with pain processing and modulation. The insular cortex (IC) plays an important role in the development and perception of the inflammatory and chronic pain. The role of the serotoninergic system in IC has not been completely studied. We used micro-dialysis in freely moving rats to determine the extracellular release of 5HT and its main metabolite (5HIAA) in the IC during an inflammatory process. Results showed an increase of extracellular levels of 5HT and 5HIAA in the IC during carrageenan-induced inflammation and this augmentation correlates with a decrease of behavioral mechanonociceptive response. Furthermore, the exogenous administration of 5HT and 5HIAA in the IC increases the nociceptive response. Our current data imply that the serotoninergic system in the IC participates in the long-term pain process.

Evaluation of the 5-HTTLPR and 5-HTTVNTR Polymorphisms in the Serotonin Transporter Gene in Women with Postpartum Depression

Objective: The purpose of the present study was to evaluate the association between the 5-HTTLPR and 5-HTTVNTR polymorphisms in the serotonin transporter gene (SLC6A4) in Brazilian women with diagnosed postpartum depression (PPD) and the presence of depressive symptoms. Method: The cohort consisted of 128 white women who were charac-terized based on skin color and morphological characteristics. The Beck Depression Inventory was used to diagnose PPD and to score the depressive symptoms. The 5-HTTLPR and 5-HTTVNTR polymorphisms were analyzed by PCR-based methods. Results: No association was observed between the PPD diagnosis and either the 5-HTTLPR (p = 0.48) or the 5-HTTVNTR (p = 0.77) polymorphism. When the polymorphisms were analyzed together with haplotype data, the analyses demonstrated that women carriers of the L-12/L-12 diplotype have lower Beck Depression Inventory scores than women carrying other diplotypes (p = 0.04). Discussion: Few studies have investigated the association of SLC6A4 polymorphisms with PPD, and the role of 5-HTTLPR and 5-HTTVNTR polymorphisms in PPD susceptibility has not been established to date. Therefore, our findings link the haplotypes of these two variants with depression symptoms, thereby contributing to our understanding of PPD susceptibility.

The antinociceptive role of central arginine vasopressin is involved in the endogenous opiate peptide, serotonin and acetylcholine systems

Our previous work has demonstrated that arginine vasopressin (AVP) plays a role in pain modulation. The present study investigated which kinds of neuropeptides and neurotransmitters in central nervous system might be involved in AVP antinociceptive role in the rat. The results showed that (1) intraventricular injection (icv) of V1 receptor antagonist [d(CH2)5Tyr(Me)AVP] and V2 receptor antagonist [d(CH2)5[D-Ile2, Ile4, Ala9-NH2]AVP] blocked the antinociceptive effect induced by AVP (icv), (2) the opiate recaptor antagonist (naloxone) reversed the antinociceptive effect induced by AVP (icv), and (3) both the serotonin receptor antagonist (cypoheptadine) and M receptor antagonist (atropine) could attenuate the antinociceptive effect induced by AVP (icv);but (4) oxytocin, dopamine, N-methyl-D-aspartate (NMDA), γ-aminobutyric acid (GABA), N, α or β receptor antagonist did not influence the antinociceptive effect induced by AVP (icv). The data suggested that AVP antinociceptive role was involved in the endogenous opiate peptide, serotonin and acetylcholine systems in central nervous system.

脑缺血中钙通道和5HT_2受体拮抗剂(S)-Emopamil的作用

缺血性脑血管病(中风)是最常见的神经障碍疾病,约占死亡数的10%。细胞“Ca^(++)超载”,是引起神经元损伤,并对此起重要作用的直接原因。已知引起“Ca(++)超载”的因素有:1.通过L-和/或N-亚型电压调节性Ca^(++)通道使Ca^(++)进入细胞的量增加;2.神经兴奋毒性氨基酸引起的Ca^(++)内流;3.激活Na^(+)-Ca^(++)交换机制(此机制可由提高细胞内Na^(+)而逆转,从而易化Ca^(++)进入细胞);4.通过非特异性的细胞膜Ca^(++)渗透作用。