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Dopamine reuptake

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https://www.readbyqxmd.com/read/29454007/destruction-of-noradrenergic-terminals-increases-dopamine-concentration-and-reduces-dopamine-metabolism-in-the-medial-prefrontal-cortex
#1
Rita Gálosi, Zoltán Petykó, Veronika Kállai, Attila Tóth, Tamás Ollmann, László Péczely, Anita Kovács, Beata Berta, László Lénárd
Effects of destroyed noradrenergic (NE) innervation in the medial prefrontal cortex (mPFC) were examined on dopamine (DA) content and metabolism. 6-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...
February 14, 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
#2
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...
February 13, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29451703/mechanisms-of-imidazoline-i-2-receptor-agonist-induced-antinociception-in-rats-involvement-of-monoaminergic-neurotransmission
#3
Justin N Siemian, Kaixuan Wang, Yanan Zhang, Jun-Xu Li
BACKGROUND AND PURPOSE: Although studies have established the antinociceptive efficacies of imidazoline I2 receptor (I2 R) agonists, its exact post-receptor mechanism remains unknown. This study tested the hypothesis that monoaminergic transmission is critical for I2 R agonist-induced antinociception. EXPERIMENTAL APPROACH: The von Frey filament test was used to examine the antinociceptive effects of the I2 R agonists 2-BFI and CR4056 on chronic constriction injury (CCI)-induced neuropathic pain or complete Freund's adjuvant (CFA)-induced inflammatory pain in rats...
February 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29451362/simultaneous-multiple-ms-binding-assays-for-the-dopamine-norepinephrine-and-serotonin-transporters
#4
Patrick Neiens, Angela De Simone, Georg Höfner, Klaus T Wanner
In this work, we present label-free, mass-spectrometry-based binding assays (MS Binding Assays), targeting the human dopamine, norepinephrine, and serotonin transporters (hDAT, hNET, and hSERT) in simultaneous binding experiments. Using a validated LC-ESI-MS/MS method for quantification of the selective dopamine transporter inhibitor (R,R)-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-ol ((R,R)-D-84), the selective norepinephrine transporter inhibitor (S,S)-reboxetine, and the selective serotonin reuptake inhibitor (S)-citalopram, binding affinities at the three monoamine transporters could be characterized simultaneously in a single binding experiment...
February 16, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29430519/heterogeneities-in-axonal-structure-and-transporter-distribution-lower-dopamine-reuptake-efficiency
#5
Cihan Kaya, Mary H Cheng, Ethan R Block, Tom M Bartol, Terrence J Sejnowski, Alexander Sorkin, James R Faeder, Ivet Bahar
Efficient clearance of dopamine (DA) from the synapse is key to regulating dopaminergic signaling. This role is fulfilled by DA transporters (DATs). Recent advances in the structural characterization of DAT from Drosophila (dDAT) and in high-resolution imaging of DA neurons and the distribution of DATs in living cells now permit us to gain a mechanistic understanding of DA reuptake events in silico. Using electron microscopy images and immunofluorescence of transgenic knock-in mouse brains that express hemagglutinin-tagged DAT in DA neurons, we reconstructed a realistic environment for MCell simulations of DA reuptake, wherein the identity, population and kinetics of homology-modeled human DAT (hDAT) substates were derived from molecular simulations...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29413521/phosphorylation-of-the-amino-terminus-of-the-dopamine-transporter-regulatory-mechanisms-and-implications-for-amphetamine-action
#6
Caline S Karam, Jonathan A Javitch
Amphetamines (AMPHs) are potent psychostimulants that are widely used and abused, with profound medical and societal impact. Their actions at dopaminergic neurons are thought to mediate their therapeutic efficacy as well as their liability for abuse and dependence. AMPHs target the dopamine transporter (DAT), the plasmalemmal membrane protein that mediates the inactivation of released dopamine (DA) through its reuptake. AMPHs act as substrates for DAT and are known to cause mobilization of dopamine (DA) to the cell exterior via DAT-mediated reverse transport (efflux)...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29413518/unique-effects-of-clozapine-a-pharmacological-perspective
#7
Jibran Y Khokhar, Angela M Henricks, Emily D K Sullivan, Alan I Green
Schizophrenia is a heterogenous and severe neuropsychiatric disorder that affects nearly 1% of the population worldwide. Antipsychotic drugs are the mainstay of treatment, but not all patients with schizophrenia respond to treatment with these agents. Clozapine, the first atypical antipsychotic, is a highly effective medication for patients with schizophrenia who do not respond to other antipsychotics. Although clozapine tends not to produce extrapyramidal symptoms, other side effects of the drug (e.g., agranulocytosis, myocarditis, seizures) limit its widespread use...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29410048/a-daily-single-dose-of-a-novel-modafinil-analogue-ce-123-improves-memory-acquisition-and-memory-retrieval
#8
Martina Kristofova, Yogesh D Aher, Marija Ilic, Bojana Radoman, Predrag Kalaba, Vladimir Dragacevic, Nilima Y Aher, Johann Leban, Volker Korz, Lisa Zanon, Winfried Neuhaus, Marcus Wieder, Thierry Langer, Ernst Urban, Harald H Sitte, Harald Hoeger, Gert Lubec, Jana Aradska
Dopamine reuptake inhibitors have been shown to improve cognitive parameters in various tasks and animal models. We recently reported a series of modafinil analogues, of which the most promising, 5-((benzhydrylsulfinyl)methyl) thiazole (CE-123), was selected for further development. The present study aims to characterize pharmacological properties of CE-123 and to investigate the potential to enhance memory performance in a rat model. In vitro transporter assays were performed in cells expressing human transporters...
February 1, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29392209/methylphenidate-attenuates-the-response-to-cold-pain-but-not-to-aversive-auditory-stimuli-in-healthy-human-a-double-blind-randomized-controlled-study
#9
Dorit Pud, Eelena Broitman, Omar Hameed, Erica Suzan, Joshua Aviram, May Haddad, Salim Hadad, Rafi Shemesh, Elon Eisenberg
Introduction: We recently showed that the psycho-stimulant norepinephrine-dopamine reuptake inhibitor methylphenidate (MP) prolonged cold pain threshold and tolerance in adults with attention-deficit hyperactivity disorder (ADHD). Objectives: The objectives of the present study were to: (1) examine whether MP has antinociceptive properties in healthy men; (2) test MP's effects on responses to aversive auditory stimuli. The underlying aim was to determine whether MP exerts antinociceptive properties or more generalized, nonspecific attenuating effects on different aversive sensory modalities...
May 2017: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/29380907/dopamine-reuptake-transporter-single-photon-emission-computed-tomography-and-transcranial-sonography-as-imaging-markers-of-prediagnostic-parkinson-s-disease
#10
Alastair J Noyce, John Dickson, Richard N Rees, Jonathan P Bestwick, Ioannis U Isaias, Marios Politis, Gavin Giovannoni, Thomas T Warner, Andrew J Lees, Anette Schrag
OBJECTIVE: The objective of this study was to examine whether prediagnostic features of Parkinson's disease (PD) were associated with changes in dopamine reuptake transporter-single-photon emission computed tomography and transcranial sonography. METHODS: Prediagnostic features of PD (risk estimates, University of Pennsylvania Smell Identification Test, Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire, and finger-tapping scores) were assessed in a large cohort of older U...
January 30, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29378209/methylphenidate-ameliorates-hypoxia-induced-mitochondrial-damage-in-human-neuroblastoma-sh-sy5y-cells-through-inhibition-of-oxidative-stress
#11
Mei Zhu, Yuan Tian, Huan Zhang, Xinxin Ma, Boxin Shang, Jiao Zhang, Yuntong Jiao, Yupeng Zhang, Jinsong Hu, Yaping Wang
AIMS: Methylphenidate (MPH) is a dopamine-reuptake inhibitor approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). Nonetheless, the cellular and molecular mechanisms of MPH are still unknown. We attempt to determine whether MPH protect neuron cells against oxidative stress by using human neuroblastoma SH-SY5Y cells. MAIN METHODS: The SH-SY5Y cells were cultured in normoxic and hypoxic conditions in the presence of different doses of MPH...
January 26, 2018: Life Sciences
https://www.readbyqxmd.com/read/29368813/selective-noradrenaline-reuptake-inhibitors-for-schizophrenia
#12
REVIEW
Paul R L Matthews, Jamie Horder, Michael Pearce
BACKGROUND: Schizophrenia is frequently a chronic and disabling illness with a heterogeneous range of symptoms. The positive symptoms usually respond to antipsychotics but the cognitive and negative symptoms of schizophrenia are difficult to treat with conventional antipsychotics and significantly impact on quality of life and social outcomes. Selective noradrenaline reuptake inhibitors (NRIs) increase prefrontal dopamine and noradrenaline levels without significantly affecting subcortical dopamine levels, making them an attractive candidate for treating cognitive and negative symptoms...
January 25, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29352029/dissociable-temporal-effects-of-bupropion-on-behavioural-measures-of-emotional-and-reward-processing-in-depression
#13
Annabel E L Walsh, Michael Browning, Wayne C Drevets, Maura Furey, Catherine J Harmer
Antidepressants remediate negative biases in emotional processing early in treatment, prior to mood improvement. However, the effects on reward processing potentially relevant to the treatment of anhedonia are less clear. Here we investigate the early and sustained effects of the dopamine and noradrenaline reuptake inhibitor bupropion on behavioural measures of emotional and reward processing in currently depressed individuals. Forty-six currently depressed patients and 42 healthy controls participated in a repeated measures study, during which open-label bupropion was administered to only the patient group over a six week period without a placebo group...
March 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29329781/dopamine-transporter-trafficking-is-regulated-by-neutral-sphingomyelinase-2-ceramide-kinase
#14
Jong Hoon Won, Seok Kyun Kim, In Chul Shin, Hae Chan Ha, Ji Min Jang, Moon Jung Back, Dae Kyong Kim
Dopamine (DA) reuptake is the primary mechanism to terminate dopaminergic transmission in the synaptic cleft. The dopamine transporter (DAT) has an important role in the regulation of DA reuptake. This study provides anatomical and physiological evidence that DAT recycling is regulated by ceramide kinase via the sphingomyelin pathway. First, the results show that DAT and neutral sphingomyelinase 2 (nSMase2) were successfully co-precipitated from striatal samples and were colocalized in the mouse striatum or PC12 cells...
January 9, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29329285/a-direct-interaction-of-cholesterol-with-the-dopamine-transporter-prevents-its-out-to-inward-transition
#15
Talia Zeppelin, Lucy Kate Ladefoged, Steffen Sinning, Xavier Periole, Birgit Schiøtt
Monoamine transporters (MATs) carry out neurotransmitter reuptake from the synaptic cleft, a key step in neurotransmission, which is targeted in the treatment of neurological disorders. Cholesterol (CHOL), a major component of the synaptic plasma membrane, has been shown to exhibit a modulatory effect on MATs. Recent crystal structures of the dopamine transporter (DAT) revealed the presence of two conserved CHOL-like molecules, suggesting a functional protein-CHOL direct interaction. Here, we present extensive atomistic molecular dynamics (MD) simulations of DAT in an outward-facing conformation...
January 12, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29289718/a-high-fat-high-sugar-western-diet-alters-dorsal-striatal-glutamate-opioid-and-dopamine-transmission-in-mice
#16
Brandon M Fritz, Braulio Muñoz, Fuqin Yin, Casey Bauchle, Brady K Atwood
Understanding neuroadaptations involved in obesity is critical for developing new approaches to treatment. Diet-induced neuroadaptations within the dorsal striatum have the capacity to drive excessive food seeking and consumption. Five week old C57BL/6J mice consumed a high-fat, high-sugar 'western diet' (WD) or a control 'standard diet' (SD) for 16 weeks. Weight gain, glucose tolerance, and insulin tolerance were measured to confirm an obese-like state. Following these 16 weeks, electrophysiological recordings were made from medium spiny neurons (MSNs) in the medial (DMS) and lateral (DLS) portions of dorsal striatum to evaluate diet effects on neuronal excitability and synaptic plasticity...
December 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/29278206/a-systematic-review-of-evidence-based-treatment-strategies-for-obsessive-compulsive-disorder-resistant-to-first-line-pharmacotherapy
#17
Umberto Albert, Donatella Marazziti, Gabriele Di Salvo, Francesca Solia, Gianluca Rosso, Giuseppe Maina
BACKGROUND: Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a significant proportion of patients do not respond satisfactorily to first-choice treatments. Several options have been investigated for the management of resistant patients. OBJECTIVE: The aim of the present paper is to systematically review the available literature concerning the strategies for the treatment of resistant adult patients with OCD...
December 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29274752/chronic-paroxetine-treatment-prevents-disruption-of-methamphetamine-sensitive-circadian-oscillator-in-a-transgenic-mouse-model-of-huntington-s-disease
#18
Koliane Ouk, Juliet Aungier, Marc Cuesta, A Jennifer Morton
Circadian abnormalities seen in Huntington's disease (HD) patients are recapitulated in several HD transgenic mouse models. In mice, alongside the master clock located in the suprachiasmatic nucleus (SCN), two other oscillators may influence circadian behaviour. These are the food-entrainable oscillator (FEO) and the methamphetamine-sensitive circadian oscillator (MASCO). SCN- and MASCO- (but not FEO-) driven rhythms are progressively disrupted in the R6/2 mouse model of HD. MASCO-driven rhythms are induced by chronic treatment with low dose of methamphetamine and characterised by an increase in period length to greater than 24 h...
December 21, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29273501/selective-%C3%AE-synuclein-knockdown-in-monoamine-neurons-by-intranasal-oligonucleotide-delivery-potential-therapy-for-parkinson-s-disease
#19
Diana Alarcón-Arís, Ariadna Recasens, Mireia Galofré, Iria Carballo-Carbajal, Nicolás Zacchi, Esther Ruiz-Bronchal, Rubén Pavia-Collado, Rosario Chica, Albert Ferrés-Coy, Marina Santos, Raquel Revilla, Andrés Montefeltro, Isabel Fariñas, Francesc Artigas, Miquel Vila, Analia Bortolozzi
Progressive neuronal death in brainstem nuclei and widespread accumulation of α-synuclein are neuropathological hallmarks of Parkinson's disease (PD). Reduction of α-synuclein levels is therefore a potential therapy for PD. However, because α-synuclein is essential for neuronal development and function, α-synuclein elimination would dramatically impact brain function. We previously developed conjugated small interfering RNA (siRNA) sequences that selectively target serotonin (5-HT) or norepinephrine (NE) neurons after intranasal administration...
November 29, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29273456/the-antipsychotic-trifluoperazine-reduces-marble-burying-behavior-in-mice-via-d2-and-5-ht2a-receptors-implications-for-obsessive-compulsive-disorder
#20
Nobuaki Egashira, Naoki Kubota, Yu Goto, Takuya Watanabe, Kaori Kubota, Shutaro Katsurabayashi, Katsunori Iwasaki
Trifluoperazine, a typical antipsychotic drug, not only antagonizes dopamine D2 receptors but also enhances serotonin 5-HT2 receptor-mediated behavior. Moreover, trifluoperazine suppresses human purinergic receptor P2X7 responses and calmodulin. However, the effect of trifluoperazine on marble-burying behavior, which has been considered an animal model of obsessive-compulsive disorder (OCD), has not been studied. Here, we examined the effect of trifluoperazine on marble-burying behavior in mice. Oral administration of paroxetine, a selective serotonin reuptake inhibitor, significantly reduced marble-burying behavior without affecting total locomotor activity...
December 19, 2017: Pharmacology, Biochemistry, and Behavior
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