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ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A （OXA）， orexin-1 receptor （OX1R）， and orexin-2 receptor （OX2R） in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine （PCPA）. Fifty BALB/c mice were randomized into a blank group， a model group， an eszopiclone （0.13 mg·kg-1） group， and low- and high-dose （8.4 and 33.6 g·kg-1， respectively） Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored， and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry （IHC） was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine （5-HT） in the hypothalamus， serum， and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus. ResultCompared with the blank group， the model group had decreased body weight （P<0.01）， increased escape latency （P<0.01）， increased sleep latency （P<0.01）， shortened sleep duration （P<0.01）， elevated OXA level and lowered 5-HT level in the hypothalamus， serum， and spleen （P<0.05）， and up-regulated mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. Compared with the model group， the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight （P<0.05， P<0.01）， shortened escape latency （P<0.05）， shortened sleep latency and prolonged sleep duration （P<0.01）， and lowered OXA level and elevated 5-HT level in the hypothalamus， serum， and spleen （P<0.05， P<0.01）. Moreover， the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.
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OBJECTIVE To evaluate the efficacy of the triple therapy of 5-HT3 receptor antagonists， neurokinin-1 receptor antagonists and dexamethasone （referred to as “triple therapy”） in the prevention and treatment of acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI and Wanfang data， randomized controlled trials （RCTs） about triple therapy or 5-HT3 receptor antagonist combined with dexamethasone （referred to as “dual therapy”） were collected during the inception to May 2023. After literature screening， data extraction and literature evaluation， network meta-analysis was performed by using Stata 16.0 software. RESULTS A total of 59 RCTs were included， involving 23 418 patients and 15 interventions. Results of network meta-analysis showed that fosaprepitant + palonosetron + dexamethasone （FPD） was most effective in terms of acute nausea and vomiting control rate， followed by fosaprepitant + granisetron + dexamethasone （FGD） and aprepitant + ramosetron + dexamethasone （AMD）. In terms of acute nausea control rate， FPD was the most effective， followed by aprepitant + palonosetron + dexamethasone （APD） and FGD. In terms of acute vomiting control rate， FPD was the most effective， followed by FGD and APD. CONCLUSIONS Fosaprepitant + palonosetron + dexamethasone is better than other triple therapy or dual therapy in preventing acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs.
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5-Hydroxytryptamine (5-HT) type 3 receptor (5-HT3R) is the only type of ligand-gated ion channel in the 5-HT receptor family. Through the high permeability of Na+, K+, and Ca2+ and activation of subsequent voltage-gated calcium channels (VGCCs), 5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system (CNS). 5-HT3Rs are widely expressed in the medial prefrontal cortex (mPFC), amygdala (AMYG), hippocampus (HIP), periaqueductal gray (PAG), and other brain regions closely associated with anxiety reactions. They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions. 5-HT3Rs mediate the activation of the cholecystokinin (CCK) system in the AMYG, and the γ-aminobutyric acid (GABA) "disinhibition" mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons (IINs). In contrast, a 5-HT3R-induced GABA "disinhibition" mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects. 5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG. This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs. However, given the circuit specific modulation of 5-HT3Rs on emotion, systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety, which deeply hinders the current clinical application of 5-HT3R drugs. Therefore, the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.
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Serotonin , Receptors, Serotonin, 5-HT3 , Anxiety , Neurons , gamma-Aminobutyric AcidABSTRACT
ObjectiveTo investigate the role of proinflammatory cytokines tumor necrosis factor alpha （TNFα） and interleukin-1β （IL-1β） in rostral ventromedial medulla （RVM） in chronic postsurgical pain （CPSP） induced by skin/muscle incision and retraction （SMIR）. MethodsSD rats were randomly divided into 5 groups： ① Sham group； ② SMIR group； ③ SMIR+TNFα/IL-1β neutralizing antibody group； ④ SMIR+TNFα/IL-1β group and ⑤ SMIR+vehicle group. 50% paw mechanical withdrawal threshold （MWT） was measured by the up-down method， immunofluroscence was used to detect the TNFα and IL-1β expression and ELISA for the 5-Hydroxytryptamine （5-HT） level. ResultsSMIR elicited persistent nociceptive sensitization， upregulated TNFα and IL-1β expression in RVM neurons and astrocytes. Microinjection of TNFα or IL-1β neutralizing antibody into RVM inhibited the development of nociceptive sensitization and decreased the level of 5-HT in both RVM and spinal dorsal horn. While microinjection of recombinant TNFα or IL-1β into RVM enhanced the development of nociceptive sensitization and increased the level of 5-HT in both RVM and spinal dorsal horn. ConclusionUp-regulation of proinflammatory cytokines in RVM may contribute to SMIR induced CPSP by promoting 5-HT release.
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ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.
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Background: Serotonin receptors 5-HT1B and 5-HT1D in the cerebral arteries are activated by the 5-hydroxytryptophan agonists (triptans) to relieve the discomfort associated with migraines. Even though triptans are often used to treat acute migraines, there is some debate over their effectiveness. Objective: Our systematic review aimed to evaluate the effectiveness of triptans for acute treatment of migraine in young individuals. Methods: Utilizing the databases of Google Scholar, Cochrane Library, and PubMed, a literature search was conducted, and all papers published till July 2022 were included. This systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. In addition to the Boolean operators AND, OR, and NOT, the following descriptive terms were also used: “Triptans,” “Pediatric Migraine,” “Migraine disorders,” “Headache,” “Children,” and “Adolescent.” Results: A total of 1047 studies were identified, and 25 articles were finally included in the study. 17 of them were RCTs while the remaining were non-randomized trials. Most studies recruited participants aged between 12-17 years. Among 25 studies, 7 reported sumatriptan use, 3 assessed a combination of sumatriptan and naproxen, 4 were on almotriptan, 1 on eletriptan, 6 on rizatriptan, and 4 on zolmitriptan use. Conclusion: We found that rizatriptan (good tolerability profile with a dose of 5 mg) and sumatriptan (nasal spray, 10 mg and 20 mg) had higher efficiency as compared to other triptans. Regardless of type or dose, all triptans are generally well tolerated by patients, but a few adverse effects such as light-headedness (sumatriptan), nasopharyngitis, and, muscular spasms (sumatriptan/ naproxen), somnolence, and dry mouth (rizatriptan), and dizziness (zolmitriptan group) were reported with the triptans.
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Depression is one of the most common psychiatric disorders with high prevalence, disability and relapse rates, and its etiology and pathogenesis are complex and still not fully understood. Neurotransmitters play a key role in maintaining chemical homeostasis in brain, and many studies have shown a strong link between neurotransmitters and the development and treatment of depression in recent years. Therefore, studying the neurotransmitters associated with depression has the potential to provide research targets and ideas for the pathogenesis and treatment strategies of depression. This paper reviews the recent domestic and foreign research results on neurotransmitter function and the pathogenesis of depression, aiming to analyze the in-depth relationship between neurotransmitter function and the pathogenesis of depression, and provide research ideas for the follow-up ex-ploration of the pathogenesis and diagnosis and treatment strategies of depression.
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The serotonin 2A receptor(5-HT
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Aim To determine the effect of histamine H
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OBJECTIVE@#To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior.@*METHODS@#Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined.@*RESULTS@#Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group.@*CONCLUSION@#Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.
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Rats , Male , Animals , Moxibustion , Rats, Sprague-Dawley , Rats, Wistar , Serotonin , Hippocampus , Dopamine , Norepinephrine , Neurotransmitter AgentsABSTRACT
ObjectiveTo investigate the mechanism of Magnolia officinalis cortex for constipation-type irritable bowel syndrome（IBS-C） rats before and after sweating. MethodIBS-C rat model was established by gavage of ice water， and rats were randomly divided into the blank group， model group， mosapride group（1 mg·kg-1）， M. officinalis cortex group（10 g·kg-1） and sweated M. officinalis cortex group（10 g·kg-1）. The changes of body weight， fecal number and fecal water content of rats were observed， 16S rRNA sequencing was used to detect the structural changes of fecal intestinal flora in rats， the levels of 5-hydroxytryptamine（5-HT） and substance P（SP） in colonic tissues of rats were determined by enzyme-linked immunosorbent assay（ELISA）. ResultCompared with the model group， the fecal water content and fecal number of mosapride group， M. officinalis cortex group and sweated M. officinalis cortex group were significantly increased（P<0.05）. At the phylum level， the top four species of flora abundance were Firmicutes， Bacteroidetes， Spirochaetes and Proteobacteria. Compared with the blank group， the proportion of Firmicutes in the model group was significantly reduced（P<0.05）， while the proportion of Spirochaetes was significantly increased（P<0.05）. Compared with the model group， the proportion of Firmicutes and Spirochaetes in M. officinalis cortex group and sweated M. officinalis cortex group tended to be similar to that in the blank group， and the proportion of Spirochaetes in sweated M. officinalis cortex group was lower than that of M. officinalis cortex group. At the family level， the top four species of flora abundance were Lactobacillaceae， S24_7， Ruminococcaceae， Bacteroidaceae， compared with the blank group， the proportion of Lactobacillaceae in the model group decreased significantly（P<0.05）， and its proportion in the M. officinalis cortex group and sweated M. officinalis cortex group increased significantly after administration（P<0.05）， and the flora structure of the two groups tended to be similar to that of the blank group. At the genus level， the top four species of flora abundance were Lactobacillus， Unspecified_S24_7， Bacteroides and Treponema. Compared with the blank group， the proportion of Lactobacillus in the model group decreased significantly（P<0.05）， while the proportion of Treponema increased significantly（P<0.05）. Compared with the model group， ratio of bacterial structure of Lactobacillus and Treponema in the M. officinalis cortex group and sweated M. officinalis cortex group tended to be similar to those in the blank group， indicating that M. officinalis cortex could restore the intestinal microbial structure of IBS-C rats before and after sweating. Compared with the model group， the 5-HT content in mosapride group was significantly reduced（P<0.05）， the contents of 5-HT and SP in the M. officinalis cortex group and sweated M. officinalis cortex group were significantly increased（P<0.01）， and the sweated M. officinalis cortex group was higher than the M. officinalis cortex group. ConclusionM. officinalis cortex can play a therapeutic role on IBS-C rats by regulating 5-HT pathway and intestinal flora structure before and after sweating.
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ObjectiveTo observe the clinical effect of modified Jichuanjian on senile patients with slow transit constipation of spleen-kidney yang deficiency syndrome and the influence on brain-gut peptide. MethodA total of 150 senile patients with slow transit constipation were randomized into control group （75 cases） and observation group （75 cases） with the random number table method. The observation group was given modified Jichuanjian （oral， 1 dose/day， 4 weeks）， and the control group was treated with Biantong Capsules （oral， 3 capsules/time， twice/day， 4 weeks）. Data before and after treatment were recorded， including the score of major constipation symptoms， score of Patient Assessment of Constipation Quality of Life （PAC-QOL）， TCM syndrome score， spontaneous complete bowel movements （SCBM）， colonic transit test， serum 5-hydroxytryptamine （5-HT）， 5-HT 4 receptor （5-HT4R）， somatostatin （SS）， and vasoactive intestinal peptide （VIP）， and recurrence. ResultThe total effective rate of the observation group was 93.06% （67/72）， as compared with the 74.65% （53/71） in the control group （χ2=8.974 6， P<0.01）. After treatment， the scores of major constipation symptoms， scores of four dimensions of PAC-QOL， total score of PAC-QOL， and TCM syndrome score were lower than those before treatment in the two groups （P<0.01）， and lower in the observation group than in the control group （P<0.01）. The SCBM in the observation group were more than those in the control group at the 2nd， 3rd， 4th weeks after treatment （P<0.01）. The proportions of residual markers at 24， 48， 72 h after treatment were smaller than those before treatment in the two groups （P<0.01）， and smaller in the observation group than in the control group （P<0.01）. After treatment， the levels of serum 5-HT and 5-HT4R were higher （P<0.01） and the levels of serum SS and VIP were lower （P<0.01） than those before treatment in the two groups. In addition， the levels of serum 5-HT and 5-HT4R in the observation group were higher （P<0.01） and the levels of serum SS and VIP were lower （P<0.01） in the observation group than in the control group. The recurrence in the observation group was 29.85% （20/67） in comparison with the 58.49% （31/53） in the control group （χ2=9.932 4， P<0.01）. ConclusionModified Jichuanjian is effective for senile patients with slow transit constipation of spleen-kidney yang deficiency syndrome， which can alleviate clinical symptoms， improve quality of life， regulate the level of serum brain-gut peptide， improve the colonic transit function， increase SCBM， and reduce the recurrence.
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OBJECTIVE@#To observe the clinical effect of bloodletting at auricular dorsal vein combined with auricular point sticking on menstrual migraine (MM) of qi stagnation and blood stasis, and explore its possible mechanism.@*METHODS@#A total of 102 cases of MM with qi stagnation and blood stasis were randomly divided into an observation group (51 cases, 3 cases dropped off) and a control group (51 cases, 2 cases dropped off). The patients in the observation group were treated with bloodletting at auricular dorsal vein combined with auricular point sticking. The bloodletting was performed at vein at upper 1/3 of the dorsalis near the ear helix; the auricular point sticking was performed at Pizhixia (AT4), Neifenmi (CO18), Jiaogan (AH6a), Nie (AT2), Zhen (AT3), Shenmen (TF4) and Yidan (CO11). The auricular points of both ears were alternate used. From 7 days before the onset of menstruation, bloodletting at auricular dorsal vein was given once every 7 days, 3 times were taken as a course of treatment, and 1 course of treatment was given; the auricular point sticking was given once every 3 days, and 6 times of treatment were given. The patients in the control group were treated with oral administration of flunarizine hydrochloride capsules. From 7 days before the onset of menstruation, flunarizine hydrochloride was given 2 capsules per time, once a day for 3 weeks. The menstrual headache index and visual analogue scale (VAS) score of the two groups were observed before treatment, one menstrual cycle into treatment and the first and the second menstrual cycle after treatment; the migraine-specific quality of life questionnaire (MSQ) score and the serum levels of estradiol (E2) and 5-hydroxytryptamine (5-HT) were compared before treatment and one menstrual cycle into treatment; the clinical efficacy was evaluated at one menstrual cycle into treatment.@*RESULTS@#Compared before treatment, the menstrual headache index and VAS scores were reduced at one menstrual cycle into treatment and the first and second menstrual cycle after treatment in the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). Compared before treatment, the MSQ scores and the serum levels of E2 and 5-HT in the two groups were increased at one menstrual cycle into treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The total effective rate was 95.8% (46/48) in the observation group, which was higher than 73.5% (36/49) in the control group (P<0.05).@*CONCLUSION@#Bloodletting at auricular dorsal vein combined with auricular point sticking could relieve headache intensity, improve the quality of life in patients with MM of qi stagnation and blood stasis, which may be achieved by raising the serum levels of E2 and 5-HT to improve the level of hormone in the body.
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Female , Humans , Acupuncture, Ear , Bloodletting , Serotonin , Capsules , Flunarizine , Qi , Quality of Life , Migraine Disorders/drug therapy , Headache/therapy , Treatment Outcome , Acupuncture PointsABSTRACT
Insomnia is a common sleep disorder without effective therapy and can affect a person's life. The mechanism of the disease is not completely understood. Hence, there is a need to understand the targets related to insomnia, in order to develop innovative therapies and new compounds. Recently, increasing interest has been focused on complementary and alternative medicines for treating or preventing insomnia. Research into their molecular components has revealed that their sedative and sleep-promoting properties rely on the interactions with various neurotransmitter systems in the brain. In this review, the role of 5-hydroxytryptamine (5-HT) in insomnia development is summarized, while a systematic analysis of studies is conducted to assess the mechanisms of herbal medicines on different 5-HT receptors subtypes, in order to provide reference for subsequent research.
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Humans , Sleep Initiation and Maintenance Disorders/drug therapy , Medicine, Chinese Traditional , Drugs, Chinese Herbal/therapeutic use , Plants, Medicinal , Receptors, Serotonin , SerotoninABSTRACT
ObjectiveTo explore the mechanism of Shaoyaotang （SYT） in the treatment of ulcerative colitis （UC） based on network pharmacology and experimental verification. MethodThe core components， target genes， and main pathways of SYT were predicted based on network pharmacology， and UC-related components， target genes， and pathways were screened. Dextran sodium sulfate （DSS） was used to induce the UC model in mice， and the effect of SYT on UC mice was observed， followed by mechanism verification. ResultNetwork pharmacology indicated that 174 active components and corresponding 159 target genes of SYT were screened， and the related pathways were those mediated by 5-hydroxytryptamine （5-HT） degredation and 5-HT receptor 3. The results of animal experiments showed that compared with the model group， the SYT group showed increased body weight and colon length（P<0.01）， reduced disease activity index （DAI） score （P<0.01）， improved histopathological manifestations， reduced concentrations of 5-HT in the colonic tissues and serum （P<0.05， P<0.01）， and increased mRNA expression of monoamine oxidase A （MAOA）， monoamine oxidase B （MAOB）， sodium-dependent serotonin transporter （SLC6A4）， and 5-HT receptor 3A （5-HTR3A） related to 5-HT metabolism in the colon （P<0.01）. ConclusionSYT can alleviate the local inflammatory response of the intestinal tract in UC by regulating 5-HT degredation pathways.
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OBJECTIVE The 5-HT2A receptor is the major target of classic hallucinogens.Both DOM(2,5-dimethoxy-4-methylamphetamine)and lisuride act at 5-HT2A receptors,and lisuride shares comparable affinity with DOM and acts as a partial agonist at 5-HT2A recep-tors.However,not like DOM,lisuride lacks hallucinogenic properties.Impulsive decision-making refers to the prefer-ence for an immediate small reinforcer(SR)over a delayed large reinforcer(LR).The current study aims to compare the effects of DOM and lisuride on impulsive decision-making and further to investigate the possible receptor mechanisms responsible for the actions of the two drugs.METHODS Impulsive decision-making was evaluated in male Sprague-Dawley rats by the percent-age of choice for the LR in delay discounting task(DDT).Delay to the LR changed in an ascending order(0,4,8,16,and 32 s)across one session.RESULTS DOM(0.3 and 0.5 mg·kg-1)increased impulsive decision-making,and the effects of DOM(0.5 mg·kg-1)was blocked by the 5-HT2A receptor antagonist ketanserin(1.0 mg·kg-1)rather than the 5-HT2C receptor antagonist SB-242084(1.0 mg·kg-1).Contrarily,lisuride(0.1,0.3 and 0.5 mg·kg-1)decreased impulsive decision-making.The effects of lisu-ride(0.3 mg·kg-1)were not antagonized by ketanserin(1.0 mg·kg-1),selective 5-HT1A antagonist WAY-100635(1.0 mg·kg-1)or selective dopamine D4 receptor antagonist L-745870(1.0 mg·kg-1),but were attenuated by the selec-tive dopamine D2/D3 receptor antagonist tiapride(40 mg·kg-1).CONCLUSION DOM and lisuride have contrasting effects on impulsive decision-making via distinct recep-tors.DOM-induced increase of impulsivity is mediated by the 5-HT2A receptor,while lisuride-induced inhibition of impulsivity is regulated by the dopamine D2/D3 receptor.
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OBJECTIVE Insomnia is the most fre-quent sleep disorder worldwide and the clinical applica-tion of therapeutic drugs has various adverse effects.In recent years,drugs developed from natural herbs have become potential alternative therapies for insomnia.Nuciferine,one of the main bioactive components obtained from the lotus leaves,has been reported to possess extensive pharmacological activities.However,its hypnotic and sleep regulatory effects have rarely been reported.Hence,this study was intended to investigate the pharma-cological effects of nuciferine and its mechanisms of action in insomnia.METHODS The hypnotic and seda-tive effects of nuciferine were investigated using the eval-uation of locomotor activity test and pentobarbital-induced sleep test in normal and serotonin(5-HT)depletion-induced insomniac mice.Furthermore,the sleep regulatory effects,including sleep time,sleep architecture,and δ-wave power spectral density,were explored using elec-troencephalography/electromyogram(EEG/EMG)-based sleep profiling in normal rats.Finally,the mechanisms of the hypnotic and sedative effects of nuciferine were explored usingin vivoand in silico experiments.RESULTS Nuciferine reduced locomotor activity and prolonged pen-tobarbital-induced sleep time in a dose-dependent man-ner in normal and insomniac model mice.Nuciferine sig-nificantly increased the total sleep time and non-rapid eye movement(NREM)sleep time,inhibited NREM sleep fragmentation,and improved delta power between 0.5 Hz and 1 Hz in normal rats.The results of molecular experiments showed that nuciferine could increase the 5-HT content and 5-HT1A receptor level in the hypothala-mus of insomnia model mice.CONCLUSION This study combined network pharmacological prediction and experi-mental pharmacological techniques to discover the seda-tive-hypnotic effect of nuciferine for the first time Nucif-erine can ameliorate sleep disorder in mice with insom-nia,possibly via serotonergic system.Nuciferine may rep-resent a novel treatment that alleviate the insomnia-like symptoms by modulating 5-HT system.
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ObjectiveTo explore the clinical effect of Tiaoxin formula in the treatment of patients with coronary heart disease and anxiety/depression and its impact on serum levels of 5-hydroxytryptamine （5-HT）， β- thromboglobulin （β-TG） and myeloperoxidase （MPO）. MethodA total of 66 patients with coronary heart disease and anxiety/depression were randomly divided into the Tiaoxin formula group and Deanxit group， 33 cases in each group. Both groups were given fundamental western treatment for coronary heart disease. Additionally， the Deanxit group was treated with flupentixol and melitracen tablets and the Tiaoxin formula group was treated with Tiaoxin Formula. The treatment lasted 8 weeks. Before and after treatment， the changes of clinical efficacy， Patient Health Questionnaire （PHQ-9）， Generalized Anxiety Disorder （GAD-7） scale， Seattle Angina Questionnaire （SAQ）， heart rate variability， and serum 5-HT， β-TG and MPO levels， and incidence of adverse reactions in the two groups were observed. ResultThere was no significant difference in the baseline indexes of patients in the two groups， and thus the two groups were comparable. After treatment for 8 weeks， the total effective rate for traditional Chinese medicine （TCM） syndromes in the Tiaoxin Formula group was 87.88% （29/33） higher than 63.64% （21/33） in the Deanxit group （Z=-2.653， P<0.05）. Compared with those before treatment， the PHQ-9 and GAD-7 scores of the two groups were decreased at week 4 and 8 of treatment （P<0.05）， and there was no statistical difference between two groups. And the SAQ dimension scores of the two groups were increased at week 4 and 8 of treatment （P<0.05）. Compared with the Deanxit group， the Tiaoxin Formula group had elevation in two dimension scores： Physical limitation and angina stability （P<0.05）. Compared with the conditions before treatment， the serum 5-HT level in the two groups were increased， while the β-TG and MPO levels were lowered （P<0.05）， and there was no distinct difference between two groups. In addition， the standard deviation of normal-to-normal intervals （SDNN） and standard deviation of average normal-to-normal intervals （SDANN） of the heart rate variability in the Tiaoxin formula group were elevated after treatment （P<0.05）， which were more significant than those of the Deanxit group （P<0.05）. During the treatment period， the incidence of adverse drug reactions in the Tiaoxin formula group was lower than that in the Deanxit group （P<0.05）， and no adverse events were observed in the two groups. ConclusionTiaoxin formula was effective for the treatment of patients with coronary heart disease accompanied by anxiety and depression， which improved the clinical symptoms， increased serum 5-HT levels， and decreased serum β-TG and MPO levels， and had few adverse reactions and high safety for patients， showing a high clinical value.
ABSTRACT
Background: Acute migraine is the most common disabling chronic neurological disorder in the world. There are a huge proportion of unmet needs in treatment efficacy and satisfaction with currently available drugs and hence need for newer agents. One such FDA-approved drug is 5-HT1F Agonist lasmiditan. Aim and Objective: The present review and meta-analysis were conducted with the objectives to analyze and review safety and efficacy of lasmiditan. Materials and Methods: Electronic database search in PUBMED and Cochrane Library was conducted using search terms ?Lasmiditan? OR ?5-HT1F Agonist.? Randomized or cross-over studies comparing safety and/or efficacy of oral lasmiditan versus other active treatment or placebo in adults with acute attack of migraine were included in the analysis. Incidences of ?2 h pain-free? events were the primary outcome measure while the incidences of adverse drug events and control of other migraine-associated symptoms were the secondary outcome measures compared. Inverse variance method and both random and fixed effect models were used in the analysis by RevMan 5.3 software. Results: At 2 h, freedom from pain (odds ratio: 2.02, 95% CI: 1.76, 2.31, n = 4395), most bothersome symptom, photophobia, and phonophobia were observed at significantly highest rates in 200 mg lasmiditan group than in placebo group. In decreasing order, incidences of dizziness, fatigue, ?1 serious adverse drug reaction, paresthesia, and somnolence were significantly higher with 200 mg lasmiditan than placebo. Conclusion: Higher the dose of lasmiditan used, rapid and stronger is its pain aborting action. Lasmiditan has effective and sustained effect up to 48 h, and hence, there is a need to analyze its potential migraine preventive effects.
ABSTRACT
Background: At present, there is an escalating concern regarding possible role of 5-HT3 receptor in psychopharmacology and the therapeutic potential of their antagonists. Moreover, inclusion of 5-HT3 receptor antagonist may curtail the antidepressant-induced LTP decrease causing memory deficits, thereby improving efficacy of current antidepressants. Aim and Objective: This study aims to evaluate the antidepressant activity of 5-HT3 antagonist, that is, ondansetron (OND) in rodent models of depression. Materials and Methods: Male Swiss albino mice (20–30 g bw) and Wistar rats (100–200 g bw) were divided into five groups. Animals received either OND p.o. (0.1, 0.5 and 1 mg/kg), venlafaxine (10 mg/kg), or vehicle (1 ml distilled water p.o.) in control. Tail suspension and forced swim test were used to evaluate the effects of drugs and control after 60 min of their administration. Furthermore, assessment of locomotor activity (LA) was done by photoactometer after 24 h of drug administration. Results: Ondansetron exhibited significant antidepressants activity (P < 0.05) in rodent models. However, LA was not significantly altered by OND. Conclusion: Ondansetron exhibited significant antidepressant activity in rodent models hence paving the way for exploration of 5-HT3 receptor antagonist in future researches and its therapeutic application in depression.