10,937 results match your criteria serotonin transporter


Synthesis and analysis of dihydrotetrabenazine derivatives as novel vesicular monoamine transporter 2 inhibitors.

Eur J Med Chem 2021 Jul 24;224:113718. Epub 2021 Jul 24.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China. Electronic address:

Vesicular monoamine transporter 2 (VMAT2) is essential for synaptic transmission of all biogenic amines in the brain including serotonin, norepinephrine, histamine, and dopamine (DA). Given its crucial role in the neurophysiology and pharmacology of the central nervous system, VMAT2 is recognized as an important therapeutic target for various neurological disorders such as tardive dyskinesia (TD). Here, a novel series of dihydrotetrabenazine derivative analogs were designed and synthesized to evaluate their effects on [H]dihydrotetrabenazine (DTBZ) binding and [H]DA uptake at VMAT2. Read More

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The Relationship between Genotype of Serotonin-transporter-linked Polymorphic Region (5-HTTLPR) and Migraine combined with Depression.

J Coll Physicians Surg Pak 2021 Aug;31(8):998-1000

Department of Psychosomatic, Mental Health Center, Zhejiang University School of Medicine, China.

The aim of this study is to explore whether there is an association between the genotype of serotonin-transporter-linked polymorphic region (5-HTTLPR) and migraine combined with depression. One hundred and sixteen patients with migraine and depressive disorder (Group A) and 116 patients with simple migraine (Group B) admitted in Mental Health Center, Zhejiang University School of Medicine, China, from January 2018 to April 2020 were included in the present study. Polymerase chain reaction (PCR) and restriction fragment length polymorphism techniques were used for detection of 5-HTTLPR genotype. Read More

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Methcathinone decreases dopamine transporter function: Role of protein kinase C.

J Neurochem 2021 Jul 28. Epub 2021 Jul 28.

Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT, USA.

Methcathinone (MCAT) is a psychostimulant of abuse that can cause both persistent striatal dopaminergic and serotonergic, as well as hippocampal serotonergic, deficits. Evidence suggests that the rapid effects of stimulants that are structurally and mechanistically similar to MCAT on monoamine transporter function may contribute to the abuse liability and/or persistent monoaminergic deficits caused by these agents. Thus, effects of MCAT on 1) striatal dopamine (DA) transporter (DAT); and 2) striatal and hippocampal serotonin transporter (SERT) function, as determined in tissues from adult male rats, were assessed. Read More

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Sex and brain region specific regulation of serotonin transporter activity in synaptosomes in guanine nucleotide-binding protein G(q) alpha knockout mice.

J Neurochem 2021 Jul 26. Epub 2021 Jul 26.

Institute of Integrative Neuroanatomy, Charité University Medicine Berlin and Max-Planck-Institute for Biophysical Chemistry Göttingen, Germany.

The regulation of the serotonin transporter (SERT) by guanine nucleotide-binding protein alpha (Gα) q was investigated using Gαq knockout mice. In the absence of Gαq, SERT mediated uptake of 5-hydroxytryptamine (5HT) was enhanced in midbrain and frontal cortex synaptosomes, but only in female mice. The mechanisms underlying this sexual dimorphism were investigated using quantitative Western blot analysis revealing brain region specific differences. Read More

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5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction.

J Clin Med 2021 Jul 14;10(14). Epub 2021 Jul 14.

Comprehensive Heart Failure Center, University Hospital of Würzburg, 97078 Würzburg, Germany.

Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Read More

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Modulation of Instagram Number of Followings by Avoidance in Close Relationships in Young Adults under a Gene x Environment Perspective.

Int J Environ Res Public Health 2021 Jul 15;18(14). Epub 2021 Jul 15.

Department of Psychology and Cognitive Science, University of Trento, 38068 Rovereto TN, Italy.

Social networking sites have determined radical changes in human life, demanding investigations on online socialization mechanisms. The knowledge acquired on in-person sociability could guide researchers to consider both environmental and genetic features as candidates of online socialization. Here, we explored the impact of the quality of adult attachment and the genetic properties of the Serotonin Transporter Gene () on Instagram social behavior. Read More

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Impacts of caffeine on resistant chicken's performance and cardiovascular gene expression.

J Anim Physiol Anim Nutr (Berl) 2021 Jul 22. Epub 2021 Jul 22.

Niewold Consultancy, Bierbeek, Belgium.

We previously reported a study on 288 broiler (Gallus gallus) chicks who received caffeine in water between days 3 and 42, at levels of 0, 6.25, 12.5, 25, 50 and 100 mg/kg body weight (BW)/day. Read More

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microRNAs and Gene-Environment Interactions in Autism: Effects of Prenatal Maternal Stress and the Gene on Maternal microRNA Expression.

Front Psychiatry 2021 5;12:668577. Epub 2021 Jul 5.

Children's Mercy Hospital and University of Missouri-Kansas City School of Medicine, Kansas City, MO, United States.

Genetics and environment both are critical in autism spectrum disorder (ASD), but their interaction (G × E) is less understood. Numerous studies have shown higher incidence of stress exposures during pregnancies with children later diagnosed with ASD. However, many stress-exposed mothers have unaffected children. Read More

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Organic Cation Transporters in Psychiatric Disorders.

Authors:
Lynette C Daws

Handb Exp Pharmacol 2021 Jul 20. Epub 2021 Jul 20.

Departments of Cellular and Integrative Physiology, and Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medications for psychiatric disorders, yet they leave the majority of patients without full symptom relief. Therefore, a major research challenge is to identify novel targets for the improved treatment of these disorders. SSRIs act by blocking the serotonin transporter (SERT), the high-affinity, low-capacity, uptake-1 transporter for serotonin. Read More

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Inhibitory control mediates the interaction between serotonin transporter gene (5-HTTLPR) and peer victimization on adolescent depressive symptoms.

Sci Rep 2021 Jul 19;11(1):14640. Epub 2021 Jul 19.

Department of Psychology, Shandong Normal University, No. 88 East Wenhua Road, Jinan, 250014, Shandong Province, China.

Many efforts have been devoted to investigating the effect of the interaction between the serotonin transporter gene (5-HTTLPR) and environment (G × E) on depression, but they yield mixed results. The inconsistency has suggested that G × E effects may be more complex than originally conceptualized, and further study is warranted. This study explored the association among 5-HTTLPR, peer victimization and depressive symptoms and the underlying mediating role of inhibitory control in this association. Read More

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The Modulatory Role of Serotonin on Human Impulsive Aggression.

Biol Psychiatry 2021 May 25. Epub 2021 May 25.

Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

The hypothesis of chronically low brain serotonin levels as pathophysiologically linked to impulsive aggression has been around for several decades. Whereas the theory was initially based on indirect methods to probe serotonin function, our understanding of the neural mechanisms involved in impulsive aggression has progressed with recent advances in neuroimaging. The review integrates evidence based on data from several neuroimaging domains in humans. Read More

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Cannabidiol and Sertraline Regulate Behavioral and Brain Gene Expression Alterations in an Animal Model of PTSD.

Front Pharmacol 2021 28;12:694510. Epub 2021 Jun 28.

Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain.

This study evaluated the effects of cannabidiol (CBD) and/or sertraline (STR) on behavioral and gene expression alterations induced by a new chronic animal model of post-traumatic stress disorder (PTSD). C57BL/6J male mice were repeatedly exposed to physical and psychogenic alternate stressful stimuli. Fear-related memory and anxiety-like behaviors were evaluated. Read More

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Sucrose Consumption Alters Serotonin/Glutamate Co-localisation Within the Prefrontal Cortex and Hippocampus of Mice.

Front Mol Neurosci 2021 28;14:678267. Epub 2021 Jun 28.

Addiction Neuroscience and Obesity Laboratory, Faculty of Health, School of Clinical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia.

The overconsumption of sugar-sweetened food and beverages underpins the current rise in obesity rates. Sugar overconsumption induces maladaptive neuroplasticity to decrease dietary control. Although serotonin and glutamate co-localisation has been implicated in reward processing, it is still unknown how chronic sucrose consumption changes this transmission in regions associated with executive control over feeding-such as the prefrontal cortex (PFC) and dentate gyrus (DG) of the hippocampus. Read More

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Association of BDNF and SERT gene polymorphisms with depression among Pakistani population.

Pak J Pharm Sci 2021 Jan;34(1):103-110

Department of Physiology, University of Karachi, Karachi, Pakistan.

Brain-derived neurotrophic factor (BDNF) and serotonin transporter (SERT) is implicated in the adverse life events which lead to depression. The variation in genetic make-up of BDNF (Val66Met) and SERT (5'-HTTLPR) are potential biomarkers in the development of neuropsychiatric disorders including depression. The purpose of this study was to investigate the correlation of functional polymorphisms of BDNF and SERT genes with depression among Pakistani population. Read More

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January 2021

Type I and type II positive allosteric modulators of α7 nicotinic acetylcholine receptors induce antidepressant-like activity in mice by a mechanism involving receptor potentiation but not neurotransmitter reuptake inhibition. Correlation with mTOR intracellular pathway activation.

Eur Neuropsychopharmacol 2021 Jul 5;52:31-47. Epub 2021 Jul 5.

Department of Pharmacology and Physiology, Oklahoma State University College of Osteopathic Medicine, Tahlequah, Oklahoma, USA. Electronic address:

The aim of this study is to determine whether type I and type II positive allosteric modulators (PAMs) of α7 nicotinic acetylcholine receptors (nAChRs) induce antidepressant-like activity in mice after acute, subchronic, and chronic treatments, and to assess whether α7-PAMs inhibit neurotransmitter transporters and activate mTOR (mammalian target of rapamycin) and/or ERK (extracellular signal-regulated protein kinases) signaling. The forced swim (FST) and tail suspension (TST) test results indicated that NS-1738 (type I PAM), PNU-120596 and PAM-2 (type II PAMs) induce antidepressant-like activity after subchronic treatment, whereas PAM-2 was also active after chronic treatment. Methyllycaconitine (α7-antagonist) inhibited the observed effects, highlighting the involvement of α7 nAChRs in this process. Read More

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Neuroinflammation and L-dopa-induced abnormal involuntary movements in 6-hydroxydopamine-lesioned rat model of Parkinson's disease are counteracted by combined administration of a 5-HT receptor agonist and A receptor antagonist.

Neuropharmacology 2021 Jul 3;196:108693. Epub 2021 Jul 3.

National Research Council of Italy (CNR), Neuroscience Institute - Cagliari, C/o Department of Biomedical Sciences, Cittadella Universitaria di Monserrato, 09042, Monserrato, CA, Italy; Department of Biomedical Sciences, Section of Neuroscience, University of Cagliari, Cittadella Universitaria di Monserrato, 09042, Monserrato, CA, Italy. Electronic address:

Several lines of evidence have strongly implicated neuroinflammation in Parkinson's disease (PD) progression and l-dopa-induced dyskinesia. The present study investigated whether early subchronic pretreatment with the serotonin 5-HT receptor agonist eltoprazine plus the adenosine A receptor antagonist preladenant counteracted l-dopa-induced abnormal involuntary movements (AIMs, index of dyskinesia), and neuroinflammation, in unilateral 6-hydroxydopamine(6-OHDA)-lesioned rat model of PD. The immunoreactivity of glial fibrillary acidic protein (GFAP), and the colocalization of ionized calcium binding adaptor molecule-1 (IBA-1), with interleukin (IL)-1β, tumor-necrosis-factor-α (TNF-α) and IL-10 were evaluated in the denervated caudate-putamen (CPu) and substantia nigra pars-compacta (SNc). Read More

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Effects of and on serotonin transporter expression in intestinal epithelial cells.

J Diabetes Metab Disord 2021 Jun 7;20(1):1-5. Epub 2021 Jan 7.

Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran.

Purpose: The highest level of peripheral serotonin in the body can be found in the gastrointestinal (GI) tract as its reservoir. There is complete interaction between human gastrointestinal microbiota and serotonin system. Serotonin in the GI is transferred by serotonin transporters (SERTs), which play a crucial role in the bioavailability of serotonin in the GI. Read More

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An Update on Medical and Surgical Treatments of Parkinson's Disease.

Aging Dis 2021 Jul 1;12(4):1021-1035. Epub 2021 Jul 1.

1Department of Neurology, Marshall University School of Medicine, Huntington, WV 25701, USA.

Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta and other neuronal populations. The worldwide prevalence of PD is over 7 million and has been increasing more rapidly than many other neurodegenerative disorders. PD symptoms can be broadly divided into motor (slowness, stiffness, tremor) and non-motor symptoms (such as depression, dementia, psychosis, orthostatic hypotension). Read More

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Hippocampal PPARα Plays a Role in the Pharmacological Mechanism of Vortioxetine, a Multimodal-Acting Antidepressant.

Front Pharmacol 2021 15;12:673221. Epub 2021 Jun 15.

Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China.

As a well-known multimodal-acting antidepressant, vortioxetine is thought to aim at several serotonin (5-HT) receptors and the 5-HT transporter. However, recently more and more proteins besides 5-HT are being reported to participate in the antidepressant mechanism of vortioxetine. As a widely known nuclear hormone receptor, peroxisome proliferator activated receptor (PPARα) possesses transcriptional activity and is very important in the brain. Read More

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Fear Extinction and Predictive Trait-Like Inter-Individual Differences in Rats Lacking the Serotonin Transporter.

Int J Mol Sci 2021 Jun 30;22(13). Epub 2021 Jun 30.

Behavioral Neuroscience, Experimental and Biological Psychology, Faculty of Psychology, Philipps-University of Marburg, Gutenberg-Str. 18, D-35032 Marburg, Germany.

Anxiety disorders are associated with a failure to sufficiently extinguish fear memories. The serotonergic system (5-hydroxytryptamine, 5-HT) with the 5-HT transporter (5-HTT, SERT) is strongly implicated in the regulation of anxiety and fear. In the present study, we examined the effects of SERT deficiency on fear extinction in a differential fear conditioning paradigm in male and female rats. Read More

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In Vitro Inhibition of Renal OCT2 and MATE1 Secretion by Antiemetic Drugs.

Int J Mol Sci 2021 Jun 16;22(12). Epub 2021 Jun 16.

Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA.

The organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) mediate the renal secretion of drugs. Recent studies suggest that ondansetron, a 5-HT antagonist drug used to prevent nausea and vomiting, can inhibit OCT2- and MATE1-mediated transport. The purpose of this study was to test the ability of five 5-HT antagonist drugs to inhibit the OCT2 and MATE1 transporters. Read More

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Assessment of Paroxetine Molecular Interactions with Selected Monoamine and γ-Aminobutyric Acid Transporters.

Int J Mol Sci 2021 Jun 11;22(12). Epub 2021 Jun 11.

Department of Organic Chemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 2 dr. A. Jurasza St., 85-094 Bydgoszcz, Poland.

Thus far, many hypotheses have been proposed explaining the cause of depression. Among the most popular of these are: monoamine, neurogenesis, neurobiology, inflammation and stress hypotheses. Many studies have proven that neurogenesis in the brains of adult mammals occurs throughout life. Read More

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Functional Characterization of the Dopaminergic Psychostimulant Sydnocarb as an Allosteric Modulator of the Human Dopamine Transporter.

Biomedicines 2021 Jun 2;9(6). Epub 2021 Jun 2.

Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.

The dopamine transporter (DAT) serves a critical role in controlling dopamine (DA)-mediated neurotransmission by regulating the clearance of DA from the synapse and extrasynaptic regions and thereby modulating DA action at postsynaptic DA receptors. Major drugs of abuse such as amphetamine and cocaine interact with DATs to alter their actions resulting in an enhancement in extracellular DA concentrations. We previously identified a novel allosteric site in the DAT and the related human serotonin transporter that lies outside the central orthosteric substrate- and cocaine-binding pocket. Read More

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Experimental Methods for Investigating Uptake 2 Processes In Vivo.

Handb Exp Pharmacol 2021 Jul 2. Epub 2021 Jul 2.

Department of Chemistry and Biochemistry, The University of South Carolina, Columbia, SC, USA.

Neuromodulators are critical regulators of the brain's signaling processes, and thus they are popular pharmacological targets for psychoactive therapies. It is clear that monoamine uptake mechanisms are complicated and subject to multiple uptake mechanisms. Uptake 1 describes uptake of the monoamine via its designated transporter (SERT for serotonin, NET for norepinephrine, and DAT for dopamine), whereas Uptake 2 details multiple transporter types on neurons and glia taking up different types of modulators, not necessarily specific to the monoamine. Read More

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The Genetics of Adverse Drug Outcomes in Type 2 Diabetes: A Systematic Review.

Front Genet 2021 14;12:675053. Epub 2021 Jun 14.

Division of Population Health and Genomics, Ninewells Hospital and School of Medicine, University of Dundee, Dundee, United Kingdom.

Adverse drug reactions (ADR) are a major clinical problem accounting for significant hospital admission rates, morbidity, mortality, and health care costs. One-third of people with diabetes experience at least one ADR. However, there is notable interindividual heterogeneity resulting in patient harm and unnecessary medical costs. Read More

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Knockout of the Serotonin Transporter in the Rat Mildly Modulates Decisional Anhedonia.

Neuroscience 2021 08 25;469:31-45. Epub 2021 Jun 25.

Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, The Netherlands.

Serotonin transporter gene variance has long been considered an essential factor contributing to depression. However, meta-analyses yielded inconsistent findings recently, asking for further understanding of the link between the gene and depression-related symptoms. One key feature of depression is anhedonia. Read More

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The Impact of Serotonin Transporter Binding Affinity on the Risk of Bleeding Related to Antidepressants.

J Clin Psychopharmacol 2021 Jul-Aug 01;41(4):470-473

From the Department of Psychiatry and Psychotherapy III, University Hospital of Ulm, Ulm.

Purpose/background: The alleged primary mechanism underlying bleeding events associated with antidepressants is inhibition of serotonin uptake in platelets resulting in reduced platelet aggregability and activity, and prolonged bleeding time. There is some evidence that a substance's degree of serotonin reuptake inhibition in terms of its binding affinity to the serotonin transporter (SERT) affects the magnitude of bleeding risk increase.

Methods/procedure: To test this hypothesis, we performed data mining in the worldwide largest pharmacovigilance database (VigiBase) and conducted pharmacodynamically informed quantitative signal detection. Read More

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The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome.

J Cell Mol Med 2021 Jun 24. Epub 2021 Jun 24.

Department of Psychiatry and Neurobehavioral Science, University College Cork, Cork, Ireland.

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Read More

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Rare Opportunities for Insights Into Serotonergic Contributions to Brain and Bowel Disorders: Studies of the SERT Ala56 Mouse.

Front Cell Neurosci 2021 3;15:677563. Epub 2021 Jun 3.

Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, United States.

Altered structure, expression, and regulation of the presynaptic serotonin (5-HT) transporter (SERT) have been associated with multiple neurobehavioral disorders, including mood disorders, obsessive-compulsive disorder (OCD), and autism spectrum disorder (ASD). Opportunities to investigate mechanistic links supporting these associations were spurred with the identification of multiple, rare human SERT coding variants in a study that established a male-specific linkage of ASD to a linkage marker on chromosome 17 which encompassed the location of the SERT gene (). We have explored the most common of these variants, SERT Ala56, and . Read More

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Female serotonin transporter-knockout rat: A potential model of irritable bowel syndrome.

FASEB J 2021 07;35(7):e21701

Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease. Although visceral hypersensitivity (VH) and disturbed gastrointestinal motility are typical pathophysiological features of IBS, the pathological mechanisms underlying this disease remain unclear. Serotonin system abnormalities are considered to play an important role in the pathomechanisms of IBS. Read More

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