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Serotonin transporter

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https://www.readbyqxmd.com/read/28445860/brephedrone-a-new-psychoactive-substance-seized-in-brazil
#1
Yuri Machado, José Coelho Neto, Paulo Eduardo Nunes Barbosa, Rogério Araújo Lordeiro, Rosemeire Brondi Alves
At the beginning of 2015, sixty-two capsules containing red-brown crystals seized in a historical city in Brazil were sent to this forensic laboratory for drug testing analysis. The material was identified as being Brephedrone, a new psychoactive substance and a bromine synthetic cathinone that is related to serotonin transportation. This substance was analyzed by ATR-FTIR, GC-MS, LC-MS, (1)H, (13)C and 2D NMR. Brephedrone apprehensions have been previously reported in Finland, France and Spain. It was the first detection of this substance in the State of Minas Gerais...
April 15, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28444137/effects-of-serotonin-transporter-gene-variation-on-impulsivity-mediated-by-default-mode-network-a-family-study-of-depression
#2
Jiook Cha, Guia Guffanti, Jay Gingrich, Ardesheer Talati, Priya Wickramaratne, Myrna Weissman, Jonathan Posner
Serotonergic neurotransmission, potentially through effects on the brain's default mode network (DMN), may regulate aspects of attention including impulse control. Indeed, genetic variants of the serotonin transporter (5-HTT) have been implicated in impulsivity and related psychopathology. Yet it remains unclear the mechanism by which the 5-HTT genetic variants contribute to individual variability in impulse control. Here, we tested whether DMN connectivity mediates an association between the 5-HTT genetic variants and impulsivity...
April 21, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28442777/serotonin-transporter-deficiency-drives-estrogen-dependent-obesity-and-glucose-intolerance
#3
Weibin Zha, Horace T B Ho, Tao Hu, Mary F Hebert, Joanne Wang
Depression and use of antidepressant medications are both associated with increased risk of obesity, potentially attributed to a reduced serotonin transporter (SERT) function. However, how SERT deficiency promotes obesity is unknown. Here, we demonstrated that SERT (-/-) mice display abnormal fat accumulation in both white and brown adipose tissues, glucose intolerance and insulin resistance while exhibiting suppressed aromatase (Cyp19a1) expression and reduced circulating 17β-estradiol levels. 17β-estradiol replacement in SERT (-/-) mice reversed the obesity and glucose intolerance, supporting a role for estrogen in SERT deficiency-associated obesity and glucose intolerance...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28434415/does-the-incredible-years-reduce-child-externalizing-problems-through-improved-parenting-the-role-of-child-negative-affectivity-and-serotonin-transporter-linked-polymorphic-region-5-httlpr-genotype
#4
Joyce Weeland, Rabia R Chhangur, Sara R Jaffee, Danielle Van Der Giessen, Walter Matthys, Bram Orobio De Castro, Geertjan Overbeek
In a randomized controlled trial, the Observational Randomized Controlled Trial of Childhood Differential Susceptibility (ORCHIDS study), we tested whether observed parental affect and observed and reported parenting behavior are mechanisms of change underlying the effects of the behavioral parent training program the Incredible Years (IY). Furthermore, we tested whether some children are more susceptible to these change mechanisms because of their temperamental negative affectivity and/or serotonin transporter linked polymorphic region (5-HTTLPR) genotype...
April 24, 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/28431168/identifying-new-susceptibility-genes-on-dopaminergic-and-serotonergic-pathways-for-the-framing-effect-in-decision-making
#5
Xiaoxue Gao, Jinting Liu, Pingyuan Gong, Junhui Wang, Wan Fang, Hongming Yan, Lusha Zhu, Xiaolin Zhou
The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing...
April 19, 2017: Social Cognitive and Affective Neuroscience
https://www.readbyqxmd.com/read/28414692/neuronal-fibers-and-neurotransmitter-receptor-expression-in-the-human-endolymphatic-sac
#6
Martin Nue Møller, Svend Kirkeby, Jonas Vikeså, Finn Cilius Nielsen, Per Cayé-Thomasen
INTRODUCTION: Recent studies suggest that the human endolymphatic sac (ES) may have multiple functions, including an ion-transport capacity comparable to the kidney, an immunological capacity and a possible natriuretic capacity. Further, there have been speculations of a yet undefined role in intracranial pressure homeostasis. The anatomical location towards the sigmoid sinus would suggest a possible endo- and/or paracrine signaling. However, neuronal connections may also apply, but it remains very scarcely explored in the human ES...
April 14, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28414050/a-study-of-time-and-sex-dependent-effects-of-vortioxetine-on-rat-sexual-behavior-possible-roles-of-direct-receptor-modulation
#7
Yan Li, Alan L Pehrson, Ronald S Oosting, Maria Gulinello, Berend Olivier, Connie Sanchez
Treatment-related sexual dysfunction is a common side effect of antidepressants and contributes to patient non-compliance or treatment cessation. However, the multimodal antidepressant, vortioxetine, demonstrates low sexual side effects in depressed patients. To investigate the mechanisms involved, sexual behavior was assessed in male and female rats after acute, and repeated (7 and 14 days) treatment with vortioxetine, flesinoxan (a 5-HT1A agonist), CP-94253 (a 5-HT1B agonist), or ondansetron (a 5-HT3 antagonist)...
April 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28412373/mechanistic-evaluation-of-tapentadol-in-reducing-the-pain-perception-using-in-vivo-brain-and-spinal-cord-microdialysis-in-rats
#8
Vijay Benade, Ramakrishna Nirogi, Gopinadh Bhyrapuneni, Saivishal Daripelli, Ganesh Ayyanki, Shantaveer Irappanavar, Ranjithkumar Ponnamaneni, Arunkumar Manoharan
Role of monoamine neurotransmitters in the modulation of emotional and pain processing in spinal cord and brain regions is not well known. Tapentadol, a norepinephrine reuptake inhibitor with µ-opioid receptor agonistic activity has recently been introduced for the treatment of moderate to severe pain. The objective of the present study was to examine the effects of tapentadol on modulation of monoamines in the prefrontal cortex and dorsal horn using brain microdialysis. Tapentadol was administered intraperitoneally at 4...
April 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28409931/1-4-18-f-fluorobenzyl-4-tetrahydrofuran-2-yl-methyl-piperazine-a-novel-suitable-radioligand-with-low-lipophilicity-for-imaging-sigma-1-receptors-in-the-brain
#9
Yingfang He, Fang Xie, Jiajun Ye, Winnie Deuther-Conrad, Bixiao Cui, Liang Wang, Jie Lu, Jörg Steinbach, Peter Brust, Yiyun Huang, Jie Lu, Hongmei Jia
We have designed and synthesized novel piperazine compounds with low lipophilicity as σ1 receptor ligands. 1-(4-Fluorobenzyl)-4-((tetrahydrofuran-2-yl)methyl)piperazine (10) possessed low nanomolar σ1 receptor affinity and high selectivity toward the vesicular acetylcholine transporter (>2000-fold), σ2 receptors (52-fold), adenosine A2A, adrenergic α2, cannabinoid CB1, dopamine D1, D2L, γ-aminobutyric acid A (GABAA), NMDA, melatonin MT1, MT2 and serotonin 5-HT1 receptors. The corresponding radiotracer [(18)F]10 demonstrated high brain uptake and extremely high brain-to-blood ratios in biodistribution studies in mice...
April 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28407315/drugs-with-antidepressant-properties-affect-tryptophan-metabolites-differently-in-rodent-models-with-depression-like-behavior
#10
Amanda Eskelund, Yan Li, David P Budac, Heidi K Müller, Gulinello Maria, Connie Sanchez, Gregers Wegener
The metabolism of tryptophan through kynurenine and serotonin pathways is linked to depression. Here, effects of different drugs with antidepressant properties (vortioxetine, fluoxetine and ketamine) on various tryptophan metabolites in different brain regions and plasma were examined using tandem mass spectrometry (LC-MS/MS), in Flinders Sensitive Line (FSL) rats, a genetic rat model of depression, and its controls: Flinders Resistant Line (FRL) and Sprague-Dawley (SD) rats. Protein levels of kynurenine pathway enzymes were measured in the brains and livers of these rat strains...
April 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28406285/serotonin-and-serotonin-transporters-in-the-adrenal-medulla-a-potential-hub-for-modulation-of-the-sympathetic-stress-response
#11
Rebecca L Brindley, Mary Beth Bauer, Randy D Blakely, Kevin P M Currie
Serotonin (5-HT) is an important neurotransmitter in the central nervous system where it modulates circuits involved in mood, cognition, movement, arousal, and autonomic function. The 5-HT transporter (SERT; SLC6A4) is a key regulator of 5-HT signaling, and genetic variations in SERT are associated with various disorders including depression, anxiety, and autism. This review focuses on the role of SERT in the sympathetic nervous system. Autonomic/sympathetic dysfunction is evident in patients with depression, anxiety, and other diseases linked to serotonergic signaling...
April 13, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28405636/when-transporters-fail-to-be-transported-how-to-rescue-folding-deficient-slc6-transporters
#12
Sonja Sucic, Ameya Kasture, H M Mazhar Asjad, Carina Kern, Ali El-Kasaby, Michael Freissmuth
The human dopamine transporter (hDAT) belongs to the solute carrier 6 (SLC6) gene family. Point mutations in hDAT (SLC6A3) have been linked to a syndrome of dopamine transporter deficiency or infantile dystonia/parkinsonism. The mutations impair DAT folding, causing retention of variant DATs in the endoplasmic reticulum and subsequently impair transport activity. The folding trajectory of DAT itself is not understood, though many insights have been gained from studies of folding-deficient mutants of the closely related serotonin transporter (SERT); i...
December 30, 2016: Journal of Neurology & Neuromedicine
https://www.readbyqxmd.com/read/28404880/serotonergic-system-antagonists-target-breast-tumor-initiating-cells-and-synergize-with-chemotherapy-to-shrink-human-breast-tumor-xenografts
#13
William D Gwynne, Robin M Hallett, Adele Girgis-Gabardo, Bojana Bojovic, Anna Dvorkin-Gheva, Craig Aarts, Kay Dias, Anita Bane, John A Hassell
Breast tumors comprise an infrequent tumor cell population, termed breast tumor initiating cells (BTIC), which sustain tumor growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC to provide more durable breast cancer remissions than are currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse BTIC resident in the mammary tumors of a HER2-overexpressing model of breast cancer. Here we report that antagonists of serotonin (5-hydroxytryptamine; 5-HT) biosynthesis and activity, including US Federal Food and Drug Administration (FDA)-approved antidepressants, targeted BTIC resident in numerous breast tumor cell lines regardless of their clinical or molecular subtype...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404690/pharmacologic-characterization-of-valbenazine-nbi-98854-and-its-metabolites
#14
Dimitri E Grigoriadis, Evan Smith, Sam R J Hoare, Ajay Madan, Haig Bozigian
The vesicular monoamine transporter 2 (VMAT2) is an integral presynaptic protein that regulates the packaging and subsequent release of dopamine and other monoamines from neuronal vesicles into the synapse. Valbenazine (NBI-98854), a novel compound that selectively inhibits VMAT2, is being developed for the treatment of tardive dyskinesia. Valbenazine is converted to two significant circulating metabolites in vivo, namely, (+)-α-dihydrotetrabenazine (R,R,R-DHTBZ) and a mono-oxy metabolite, NBI-136110. Radioligand binding studies were conducted to assess and compare valbenazine, tetrabenazine and their respective metabolites in their abilities to selectively and potently inhibit [(3)H]-DHTBZ binding to VMAT2 in rat striatal, rat forebrain, and human platelet homogenates...
April 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28396142/atypical-binding-at-dopamine-and-serotonin-transporters-contribute-to-the-discriminative-stimulus-effects-of-mephedrone
#15
Alyssa F DeLarge, Laura L Erwin, Peter J Winsauer
Mephedrone (4-methylmethcathinone), a constituent of the recreational substances known as "bath salts", is a synthetic cathinone that can produce auditory and visual hallucinations, as well as problematic cardiovascular effects. This study compared the discriminative stimulus effects of mephedrone (0.32-10 mg/kg) with other prototypical drugs of abuse: cocaine (0.56-32 mg/kg), d-amphetamine (0.18-3.2 mg/kg), ketamine (1.8-18 mg/kg), phencyclidine (PCP, 1-5.6 mg/kg), heroin (1-10 mg/kg), 2,5-dimethoxy-4-iodoamphetamine (R-DOI, 0...
April 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28391970/novel-5-ht7r-antagonists-arylsulfonamide-derivatives-of-aryloxy-propyl-piperidines-add-on-effect-to-the-antidepressant-activity-of-ssri-and-dri-and-pro-cognitive-profile
#16
Vittorio Canale, Anna Partyka, Rafał Kurczab, Martyna Krawczyk, Tomasz Kos, Grzegorz Satała, Bartłomiej Kubica, Magdalena Jastrzębska-Więsek, Anna Wesołowska, Andrzej J Bojarski, Piotr Popik, Paweł Zajdel
A novel series of arylsulfonamide derivatives of (aryloxy)propyl piperidines was designed to obtain potent 5-HT7R antagonists. Among the compounds evaluated herein, 3-chloro-N-{1-[3-(1,1-biphenyl-2-yloxy)2-hydroxypropyl]piperidin-4-yl}benzenesulfonamide (25) exhibited antagonistic properties at 5-HT7R and showed selectivity over selected serotoninergic and dopaminergic receptors, as well as over serotonin, noradrenaline and dopamine transporters. Compound 25 demonstrated significant antidepressant-like activity in the forced swim test (0...
May 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28391138/associations-between-serotonin-transporter-and-behavioral-traits-and-diagnoses-related-to-anxiety
#17
Ardesheer Talati, Zagaa Odgerel, Priya J Wickramaratne, Andrea Norcini Pala, Jamie L Skipper, Jay A Gingrich, Myrna M Weissman
The role of the serotonin transporter promoter-linked polymorphism (5-HTTLPR) in psychiatric disease remains unclear. Behavioral traits could serve as alternative outcomes that are stable, precede psychopathology, and capture more sub-clinical variation. We test associations between 5-HTTLPR and (1) behavioral traits and (2) clinical diagnoses of anxiety and depression. Second and third generation participants (N=203, 34.2±13.8 years, 54% female) at high- or low- familial risk for depression (where risk was defined by the presence of major depression in the 1st generation) were assessed longitudinally using the Schedule for Affective Disorders and Schizophrenia-lifetime interview, Barratt Impulsiveness Scale-11, Buss-Perry Aggression Questionnaire, and the NEO-Five Factor Inventory...
March 21, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28385052/perinatal-ssri-exposure-permanently-alters-cerebral-serotonin-receptor-mrna-in-mice-but-does-not-impact-adult-behaviors
#18
Lauritz R Meyer, Benjamin Dexter, Cecilia Lo, Elizabeth Kenkel, Takahito Hirai, Robert D Roghair, Sarah E Haskell
PURPOSE: Associations have been made between maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy and altered behavior in offspring, including an increased risk of autism. Given the important role serotonin plays in behavior, we hypothesized SSRI exposure in the perinatal period would alter central serotonin receptor expression and program adult behaviors in mice. METHODS: Female mice were injected with sertraline or saline throughout pregnancy...
April 24, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28383321/antidepressive-like-effect-of-imperatorin-from-angelica-dahurica-in-prenatally-stressed-offspring-rats-through-5-hydroxytryptamine-system
#19
Yanjun Cao, Jiahui Liu, Qiong Wang, Minghui Liu, Ying Cheng, Xiaoxiao Zhang, Tianwei Lin, Zhongliang Zhu
Adolescence is a time of continued brain maturation, particularly in limbic and cortical regions, which undoubtedly plays a role in the physiological and emotional changes. Prenatally stressed offspring rats were used to investigate the potential antidepressive-like effects of imperatorin (IMP) extracted from the root of radix angelica. After 4 weeks of treatment of IMP, behavioral tests (sucrose-preference test, forced-swimming test, and open-field test) were measured. 5-hydroxytryptamine (5-HT) concentration in the hippocampus and frontal cortex was measured using an enzyme-linked immunosorbent assay...
May 24, 2017: Neuroreport
https://www.readbyqxmd.com/read/28379618/association-between-serotonin-denervation-and-resting-state-functional-connectivity-in-mild-cognitive-impairment
#20
Frederick S Barrett, Clifford I Workman, Haris I Sair, Alena V Savonenko, Michael A Kraut, Devin J Sodums, Jin J Joo, Najlla Nassery, Christopher M Marano, Cynthia A Munro, Jason Brandt, Yun Zhou, Dean F Wong, Gwenn S Smith
Resting-state functional connectivity alterations have been demonstrated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) before the observation of AD neuropathology, but mechanisms driving these changes are not well understood. Serotonin neurodegeneration has been observed in MCI and AD and is associated with cognitive deficits and neuropsychiatric symptoms, but the role of the serotonin system in relation to brain network dysfunction has not been a major focus of investigation. The current study investigated the relationship between serotonin transporter availability (SERT; measured using positron emission tomography) and brain network functional connectivity (measured using resting-state functional MRI) in 20 participants with MCI and 21 healthy controls...
April 5, 2017: Human Brain Mapping
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