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https://www.readbyqxmd.com/read/29891587/characterization-of-the-neurochemical-and-behavioral-effects-of-solriamfetol-jzp-110-a-selective-dopamine-and-norepinephrine-reuptake-inhibitor
#1
Michelle G Baladi, Michael J Forster, Michael B Gatch, Richard B Mailman, Danielle L Hyman, Lawrence P Carter, Aaron J Janowsky
Excessive sleepiness (ES) is associated with several sleep disorders, including narcolepsy and obstructive sleep apnea (OSA). A role for monoaminergic systems in treating these conditions is highlighted by the clinical use of United States Food and Drug Administration-approved drugs that act on these systems, such as dextroamphetamine, methylphenidate, modafinil, and armodafinil. Solriamfetol (JZP-110) is a wake-promoting agent that is currently being evaluated to treat ES in patients with narcolepsy or OSA...
June 11, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29888303/chronic-social-stress-induces-peripheral-and-central-immune-activation-blunted-mesolimbic-dopamine-function-and-reduced-reward-directed-behaviour-in-mice
#2
Giorgio Bergamini, Jonas Mechtersheimer, Damiano Azzinnari, Hannes Sigrist, Michaela Buerge, Robert Dallmann, Robert Freije, Afroditi Kouraki, Jolanta Opacka-Juffry, Erich Seifritz, Boris Ferger, Tobias Suter, Christopher R Pryce
Psychosocial stress is a major risk factor for depression, stress leads to peripheral and central immune activation, immune activation is associated with blunted dopamine (DA) neural function, DA function underlies reward interest, and reduced reward interest is a core symptom of depression. These states might be inter-independent in a complex causal pathway. Whilst animal-model evidence exists for some specific steps in the pathway, there is currently no animal model in which it has been demonstrated that social stress leads to each of these immune, neural and behavioural states...
February 2018: Neurobiology of Stress
https://www.readbyqxmd.com/read/29875227/tas-303-a-novel-selective-norepinephrine-reuptake-inhibitor-that-increases-urethral-pressure-in-rats-indicating-its-potential-as-a-therapeutic-agent-for-stress-urinary-incontinence
#3
Hiroya Mizutani, Fukumitsu Sakakibara, Masahito Komuro, Eiji Sasaki
Stress urinary incontinence (SUI) is characterized by involuntary leakage associated with exertion, effort, sneezing, coughing, or lifting. Duloxetine, a serotonin norepinephrine reuptake inhibitor, is approved for the treatment of patients with SUI in some European countries, but not in the USA. There is currently no globally approved pharmacological drug for the treatment of SUI patients. Therefore, a new pharmacological treatment option is required. TAS-303 is a novel small-molecule selective norepinephrine reuptake inhibitor that displays significant norepinephrine transporter (NET) inhibitory activity toward the serotonin or dopamine transporters...
June 6, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29872404/silencing-of-syntaxin-1a-in-the-dopaminergic-neurons-decreases-the-activity-of-the-dopamine-transporter-and-prevents-amphetamine-induced-behaviors-in-c-elegans
#4
Ambra Lanzo, Bryan D Safratowich, Sirisha R Kudumala, Ivan Gallotta, Giuseppina Zampi, Elia Di Schiavi, Lucia Carvelli
The dopamine transporter (DAT) is a cell membrane protein whose main function is to reuptake the dopamine (DA) released in the synaptic cleft back into the dopaminergic neurons. Previous studies suggested that the activity of DAT is regulated by allosteric proteins such as Syntaxin-1A and is altered by drugs of abuse such as amphetamine (Amph). Because Caenorhabditis elegans expresses both DAT (DAT-1) and Syntaxin-1A (UNC-64), we used this model system to investigate the functional and behavioral effects caused by lack of expression of unc-64 in cultured dopaminergic neurons and in living animals...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29803894/impact-of-selective-serotonin-reuptake-inhibitors-ssris-during-pregnancy-and-lactation-a-focus-on-short-and-long-term-vascular-effects
#5
REVIEW
S Zullino, T Simoncini
SSRIs are the first choice for the treatment of mood disorders during pregnancy and lactation. Despite the known side effects, the benefits/risks balance suggests their use. Hypertensive disorders of pregnancy (HDP) and Intrauterine growth restriction (IUGR) are the main vascular effects of these drugs, with mechanisms that involves endothelial dysfunction in feto-placental system. These data are supported by animal models, even if preliminary findings are not yet adequately supported by molecular and clinical data...
May 24, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/29802841/monoaminergic-and-aminoacidergic-receptors-are-involved-in-the-antidepressant-like-effect-of-ginsenoside-rb1-in-mouse-hippocampus-ca3-and-prefrontal-cortex
#6
Guo-Li Wang, Ying-Ping Wang, Jing-Yu Zheng, Lian-Xue Zhang
Ginsenoside Rb1 (Rb1), as the major bioactive ingredient of Panax ginseng C.A. Meyer, elicited a novel antidepressant-like effect in the forced swim test (FST) in chronic unpredictable mild stress (CUMS) rats in our previous study. To further explore the molecular mechanism of Rb1 on the neurotransmitters such as 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), norepinephrine (NE), dopamine (DA), homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), glutamate (Glu) and gamma-aminobutyric acid (GABA) in this antidepressant-like effect, the neurochemical changes in the monoaminergic and aminoacidergic receptors were investigated in the present pharmacological study by using reuptake inhibitors, receptors agonists and antagonists...
May 23, 2018: Brain Research
https://www.readbyqxmd.com/read/29801770/-consequences-of-the-monoaminergic-systems-cross-talk-in-the-antidepressant-activity
#7
L Tritschler, R Gaillard, A M Gardier, D J David, J-P Guilloux
Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressant treatment for treat major depressive disorders. Despite their effectiveness, only 30% of SSRI-treated patients reach remission of depressive symptoms. SSRIs by inhibiting the serotonin transporter present some limits with residual symptoms. Increasing not only serotonin but also norepinephrine and dopamine levels in limbic areas seems to improve remission. Anatomical relationships across serotoninergic, dopaminergic and noradrenergic systems suggest tight reciprocal regulations among them...
May 22, 2018: L'Encéphale
https://www.readbyqxmd.com/read/29789702/parallel-descending-dopaminergic-connectivity-of-a13-cells-to-the-brainstem-locomotor-centers
#8
Sandeep Sharma, Linda H Kim, Kyle A Mayr, David A Elliott, Patrick J Whelan
The mesencephalic locomotor region (MLR) is an important integrative area for the initiation and modulation of locomotion. Recently it has been realized that dopamine (DA) projections from the substantia nigra pars compacta project to the MLR. Here we explore DA projections from an area of the medial zona incerta (ZI) known for its role in motor control onto the MLR. We provide evidence that dopaminergic (DAergic) A13 neurons have connectivity to the cuneiform nucleus (CnF) and pedunculopontine tegmental nucleus (PPTg) of the MLR...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29740748/the-effects-of-chronic-amitriptyline-on-zebrafish-behavior-and-monoamine-neurochemistry
#9
Darya A Meshalkina, Elana V Kysil, Kristina A Antonova, Konstantin A Demin, Tatiana O Kolesnikova, Sergey L Khatsko, Raul R Gainetdinov, Polina A Alekseeva, Allan V Kalueff
Amitriptyline is a commonly used tricyclic antidepressant (TCA) inhibiting serotonin and norepinephrine reuptake. The exact CNS action of TCAs remains poorly understood, necessitating new screening approaches and novel model organisms. Zebrafish (Danio rerio) are rapidly emerging as a promising tool for pharmacological research of antidepressants, including amitriptyline. Here, we examine the effects of chronic 2-week exposure to 10 and 50 μg/L amitriptyline on zebrafish behavior and monoamine neurotransmitters...
May 8, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29729893/memantine-ameliorates-depressive-like-behaviors-by-regulating-hippocampal-cell-proliferation-and-neuroprotection-in-olfactory-bulbectomized-mice
#10
Kohei Takahashi, Osamu Nakagawasai, Wataru Nemoto, Shogo Kadota, Jinichi Isono, Takayo Odaira, Wakana Sakuma, Yuichiro Arai, Takeshi Tadano, Koichi Tan-No
Our previous study suggested that the non-competitive N-methyl-d-aspartate receptor antagonist memantine (MEM) inhibits dopamine (DA) reuptake and turnover by inhibiting brain monoamine oxidase. Clinical studies have reported that MEM may improve depressive symptoms; however, specific mechanisms underlying this effect are unclear. We performed emotional behavior, tail suspension, and forced swimming tests to examine whether MEM has antidepressant effects in olfactory bulbectomized (OBX) mice, an animal model of depression...
May 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29692706/the-relationship-between-dopamine-neurotransmitter-dynamics-and-the-blood-oxygen-level-dependent-bold-signal-a-review-of-pharmacological-functional-magnetic-resonance-imaging
#11
REVIEW
Tyler J Bruinsma, Vidur V Sarma, Yoonbae Oh, Dong Pyo Jang, Su-Youne Chang, Greg A Worrell, Val J Lowe, Hang Joon Jo, Hoon-Ki Min
Functional magnetic resonance imaging (fMRI) is widely used in investigations of normal cognition and brain disease and in various clinical applications. Pharmacological fMRI (pharma-fMRI) is a relatively new application, which is being used to elucidate the effects and mechanisms of pharmacological modulation of brain activity. Characterizing the effects of neuropharmacological agents on regional brain activity using fMRI is challenging because drugs modulate neuronal function in a wide variety of ways, including through receptor agonist, antagonist, and neurotransmitter reuptake blocker events...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29675596/post-finasteride-syndrome-and-post-ssri-sexual-dysfunction-two-sides-of-the-same-coin
#12
REVIEW
Silvia Giatti, Silvia Diviccaro, Giancarlo Panzica, Roberto Cosimo Melcangi
Sexual dysfunction is a clinical condition due to different causes including the iatrogenic origin. For instance, it is well known that sexual dysfunction may occur in patients treated with antidepressants like selective serotonin reuptake inhibitors (SSRI). A similar side effect has been also reported during treatment with finasteride, an inhibitor of the enzyme 5alpha-reductase, for androgenetic alopecia. Interestingly, sexual dysfunction persists in both cases after drug discontinuation. These conditions have been named post-SSRI sexual dysfunction (PSSD) and post-finasteride syndrome (PFS)...
April 19, 2018: Endocrine
https://www.readbyqxmd.com/read/29578004/the-triple-monoamine-re-uptake-inhibitor-dov-216-303-promotes-functional-recovery-after-spinal-cord-contusion-injury-in-mice
#13
Tak-Ho Chu, Karen Cummins, Peter K Stys
Serotonin, noradrenaline and dopamine are important neuromodulators for locomotion in the spinal cord. Disruption of descending axons after spinal cord injury resulted in reduction of excitatory and neuromodulatory inputs to spinal neurons for locomotion. Receptor agonists or reuptake inhibitors for these neuromodulators have been shown to be beneficial in incomplete spinal cord injury. In this study, we tested a triple re-uptake inhibitor, DOV 216,303, for its ability to affect motor function recovery after spinal cord injury in mice...
May 14, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29574296/novel-prodrug-prx-p4-003-selectively-activated-by-gut-enzymes-may-reduce-the-risk-of-iatrogenic-addiction-and-abuse
#14
Sandeep T Patil, Ron H Bihovsky, Steven A Smith, William Z Potter, Valentino J Stella
OBJECTIVES: Prescription stimulants are vulnerable to oral and parenteral abuse. Intravenous forms of abuse may be most detrimental due to an enhanced risk of dependence, overdose, and infectious diseases. Our objective was to discover an orally active prodrug of a stimulant that would not be easily converted to its parent when injected, thus hindering intravenous abuse. METHODS: Following an initial analysis of stimulant structures, the fencamfamine isomer [(-)-FCF; (N-ethyl-3-phenylbicyclo[2...
May 1, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29507426/exercise-ameliorates-motor-deficits-and-improves-dopaminergic-functions-in-the-rat-hemi-parkinson-s-model
#15
Yuan-Hao Chen, Tung-Tai Kuo, Jen-Hsin Kao, Eagle Yi-Kung Huang, Tsung-Hsun Hsieh, Yu-Ching Chou, Barry J Hoffer
To determine the influences of exercise on motor deficits and dopaminergic transmission in a hemiparkinson animal model, we measured the effects of exercise on the ambulatory system by estimating spatio-temporal parameters during walking, striatal dopamine (DA) release and reuptake and synaptic plasticity in the corticostriatal pathway after unilateral 6-OHDA lesions. 6-OHDA lesioned hemiparkinsonian rats were exercised on a fixed speed treadmill for 30 minutes per day. Controls received the same lesion but no exercise...
March 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29483349/benefits-and-limitations-of-drug-studies-in-temperament-research-biochemical-responses-as-indicators-of-temperament
#16
REVIEW
Petra Netter
This paper presents a discussion of principles and problems of neurotransmitter challenge tests using examples of experiments, most of which were performed in the author's laboratory. Drugs targeting synthesis, release, receptors or reuptake of dopamine, serotonin and noradrenergic transmitter (TM) systems were used for characterizing or discriminating certain temperament or personality traits and their sub-factors. Any personality or temperament trait is characterized by multiple TM responses, thus constellations of hormone responses to drugs acting on different TM systems or on different sources of TM activity were investigated within individuals in crossover designs...
April 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29482023/dopaminergic-dysregulation-and-impaired-associative-learning-behavior-in-zebrafish-during-chronic-dietary-exposure-to-selenium
#17
Mohammad Naderi, Arash Salahinejad, Maud C O Ferrari, Som Niyogi, Douglas P Chivers
A growing body of evidence indicates that exposure to selenium (Se) can cause neurotoxicity, and this can occur because of its interference with several neurotransmitter systems in humans and animals. Dopamine is a critical modulator of a variety of brain functions and a prime target for environmental neurotoxicants. However, effects of environmentally relevant concentrations of Se on dopaminergic system and its neurobehavioral effects are still largely unknown. For this purpose, we exposed zebrafish, a model organism, to different concentrations of dietary l-selenomethionine (control, 3...
June 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29480715/scalable-nanostructured-carbon-electrode-arrays-for-enhanced-dopamine-detection
#18
Silvia Demuru, Luca Nela, Nathan Marchack, Steven J Holmes, Damon B Farmer, George S Tulevski, Qinghuang Lin, Hariklia Deligianni
Dopamine is a neurotransmitter that modulates arousal and motivation in humans and animals. It plays a central role in the brain "reward" system. Its dysregulation is involved in several debilitating disorders such as addiction, depression, Parkinson's disease, and schizophrenia. Dopamine neurotransmission and its reuptake in extracellular space takes place with millisecond temporal and nanometer spatial resolution. Novel nanoscale electrodes are needed with superior sensitivity and improved spatial resolution to gain an improved understanding of dopamine dysregulation...
April 27, 2018: ACS Sensors
https://www.readbyqxmd.com/read/29454007/destruction-of-noradrenergic-terminals-increases-dopamine-concentration-and-reduces-dopamine-metabolism-in-the-medial-prefrontal-cortex
#19
Rita Gálosi, Zoltán Petykó, Veronika Kállai, Attila Tóth, Tamás Ollmann, László Péczely, Anita Kovács, Beáta Berta, László Lénárd
Effects of destroyed noradrenergic (NE) innervation in the medial prefrontal cortex (mPFC) were examined on dopamine (DA) content and metabolism. Six-hydroxy-DOPA (6-OHDOPA) or 6-hydroxy-dopamine (6-OHDA) in combination with a potent DA reuptake inhibitor GBR 12935 or 6-OHDA were injected bilaterally into the mPFC in separate groups of animals. In addition, GBR 12935 or vehicle was injected into the mPFC in two other groups of animals as control experiments. NE and DA concentrations from postmortem tissue of the mPFC were measured using HPLC with electrochemical detection...
May 15, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29452175/replacement-treatment-during-extinction-training-with-the-atypical-dopamine-uptake-inhibitor-jhw-007-reduces-relapse-to-methamphetamine-seeking
#20
Ashlea F Dassanayake, Juan J Canales
There are currently no approved medications to effectively counteract the effects of methamphetamine (METH), reduce its abuse and prolong abstinence from it. Data accumulated in recent years have shown that a range of N-substituted benztropine (BZT) analogues possesses psychopharmacological features consistent with those of a potential replacement or "substitute" treatment for stimulant addiction. On the other hand, the evidence that antidepressant therapy may effectively prevent relapse to stimulant seeking is controversial...
April 3, 2018: Neuroscience Letters
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