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https://www.readbyqxmd.com/read/28110353/a-role-for-sigma-receptors-in-stimulant-self-administration-and-addiction
#1
Jonathan L Katz, Takato Hiranita, Weimin C Hong, Martin O Job, Christopher R McCurdy
Sigma receptors (σRs) are structurally unique proteins that function intracellularly as chaperones. Historically, σRs have been implicated as modulators of psychomotor stimulant effects and have at times been proposed as potential avenues for modifying stimulant abuse. However, the influence of ligands for σRs on the effects of stimulants, such as cocaine or methamphetamine, in various preclinical procedures related to drug abuse has been varied. The present paper reviews the effects of σR agonists and antagonists in three particularly relevant procedures: stimulant discrimination, place conditioning, and self-administration...
January 22, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28106567/fractional-anisotropy-and-mean-diffusion-as-measures-of-dopaminergic-function-in-parkinson-s-disease-challenging-results
#2
Niklas Lenfeldt, Johan Eriksson, Björn Åström, Lars Forsgren, Susanna Jakobson
BACKGROUND: Diffusion tensor imaging (DTI) has been purported as an imaging technique to assess dopaminergic degeneration in Parkinson's disease. OBJECTIVE: To test if fractional anisotropy (FA) and mean diffusion (MD) in the basal ganglia as measured by DTI correlates with dopaminergic function as measured by dopamine transporter (DAT) and dopamine D2-receptor (D2R) SPECT. METHODS: One-hundred and eleven patients with Parkinson's disease (71±10 years) and thirty-one controls (68±7 years) performed DTI, DAT and D2R SPECT at baseline and four follow-ups (1-year: 89 patients/zero controls; 3-year: 72/11; 5-year: 48/17; and 8-year: 13/13)...
January 17, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28103426/analytical-characterization-and-pharmacological-evaluation-of-the-new-psychoactive-substance-4-fluoromethylphenidate-4%C3%A2-f-mph-and-differentiation-between-the-%C3%A2-threo-and-%C3%A2-erythro-diastereomers
#3
Gavin McLaughlin, Noreen Morris, Pierce V Kavanagh, John D Power, Geraldine Dowling, Brendan Twamley, John O'Brien, Gary Hessman, Brian Murphy, Donna Walther, John S Partilla, Michael H Baumann, Simon D Brandt
Misuse of (±)-threo-methylphenidate (methyl-2-phenyl-2-(piperidin-2-yl)acetate; Ritalin®, MPH) has long been acknowledged, but the appearance of MPH analogs in the form of 'research chemicals' has only emerged in more recent years. 4-Fluoromethylphenidate (4 F-MPH) is one of these recent examples and this study presents the identification and analytical characterization of two powdered 4 F-MPH products that were obtained from an online vendor in 2015. Interestingly, the products appeared to have originated from two distinct batches given that one product consisted of (±)-threo-4 F-MPH isomers whereas the second sample consisted of a mixture of (±)-threo and (±)-erythro 4 F-MPH...
January 19, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28096470/dampened-amphetamine-stimulated-behavior-and-altered-dopamine-transporter-function-in-the-absence-of-brain-gdnf
#4
Jaakko Kopra, Anne Panhelainen, Sara Af Bjerkén, Lauriina Porokuokka, Kärt Varendi, Soophie Olfat, Heidi Montonen, T Petteri Piepponen, Mart Saarma, Jaan-Olle Andressoo
: Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases including drug addiction and Parkinson's disease. Because of its well-established dopaminotrophic effects, the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) has been extensively studied in various disorders with disturbed dopamine homeostasis. The outcomes from pre-clinical and clinical studies vary, however, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function...
January 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28096460/occupancy-of-the-zinc-binding-site-by-transition-metals-decreases-the-substrate-affinity-of-the-human-dopamine-transporter-by-an-allosteric-mechanism
#5
Yang Li, Felix P Mayer, Peter S Hasenhuetl, Verena Burtscher, Klaus Schicker, Harald H Sitte, Michael Freissmuth, Walter Sandtner
The human dopamine transporter (DAT) has a tetrahedral Zn(2+)-binding site. Zn(2+)-binding sites are also recognized by other first row transition metals. Excessive accumulation of manganese or of copper can lead to Parkinsonism due to dopamine deficiency. Accordingly, we examined the effect of Mn(2+), Co(2+), Ni(2+) and Cu(2+)on transport-associated currents through DAT and DAT-H193K, a mutant with a disrupted Zn(2+)-binding site. All transition metals - but Mn(2+) - modulated the transport cycle of wild type DAT with affinities in the low µM range...
January 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28094812/putative-presynaptic-dopamine-dysregulation-in-schizophrenia-is-supported-by-molecular-evidence-from-post-mortem-human-midbrain
#6
T D Purves-Tyson, S J Owens, D A Rothmond, G M Halliday, K L Double, J Stevens, T McCrossin, C Shannon Weickert
The dopamine hypothesis of schizophrenia posits that increased subcortical dopamine underpins psychosis. In vivo imaging studies indicate an increased presynaptic dopamine synthesis capacity in striatal terminals and cell bodies in the midbrain in schizophrenia; however, measures of the dopamine-synthesising enzyme, tyrosine hydroxylase (TH), have not identified consistent changes. We hypothesise that dopamine dysregulation in schizophrenia could result from changes in expression of dopamine synthesis enzymes, receptors, transporters or catabolic enzymes...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28093210/neuroprotection-by-paeoniflorin-in-the-mptp-mouse-model-of-parkinson-s-disease
#7
Meizhu Zheng, Chunming Liu, Yajun Fan, Pan Yan, Dongfang Shi, Yuchi Zhang
Paeoniflorin (PF) is a major bioactive ingredient in Radix Paeonia alba roots that has low toxicity and has been shown to have neuroprotective effects. Our in vitro experiments suggested that PF affords a significant neuroprotective effect against MPP(+)-induced damage and apoptosis in PC12 cells through Bcl-2/Bax/caspase-3 pathway. The objectives of the present study were to explore the potential neuroprotective effect of PF in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD)...
January 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28075498/tamoxifen-and-its-active-metabolites-inhibit-dopamine-transporter-function-independently-of-the-estrogen-receptors
#8
Sarah R Mikelman, Bipasha Guptaroy, Margaret Gnegy
As one of the primary mechanisms by which dopamine signaling is regulated, the dopamine transporter (DAT) is an attractive pharmacological target for the treatment of diseases based in dopaminergic dysfunction. In this work we demonstrate for the first time that the commonly prescribed breast cancer therapeutic tamoxifen and its major metabolites, 4-hydroxytamoxifen and endoxifen, inhibit DAT function. Tamoxifen inhibits [(3) H]dopamine uptake into hDAT-N2A cells via an uncompetitive or mixed mechanism. Endoxifen, an active metabolite of tamoxifen, asymmetrically inhibits DAT function in hDAT-N2A cells, showing a preference for the inhibition of amphetamine-stimulated dopamine efflux as compared to dopamine uptake...
January 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28075189/11-analytically-confirmed-cases-of-mexedrone-use-among-polydrug-users
#9
Liam Roberts, Loretta Ford, Neel Patel, J Allister Vale, Sally M Bradberry
INTRODUCTION: Mexedrone, 3-methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one, is the alpha-methoxy-derivative of mephedrone (4-methyl-N-methyl cathinone). Mexedrone inhibits the re-uptake of serotonin and dopamine in a dose-dependent manner and has affinity for serotonin and dopamine membrane transporters and receptors (5-HT2 and D2 receptors), producing sympathomimetic effects similar to amfetamines. To date there are no published clinical reports on mexedrone use that are analytically confirmed...
January 11, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28072417/dopaminergic-dynamics-underlying-sex-specific-cocaine-reward
#10
Erin S Calipari, Barbara Juarez, Carole Morel, Deena M Walker, Michael E Cahill, Efrain Ribeiro, Ciorana Roman-Ortiz, Charu Ramakrishnan, Karl Deisseroth, Ming-Hu Han, Eric J Nestler
Although both males and females become addicted to cocaine, females transition to addiction faster and experience greater difficulties remaining abstinent. We demonstrate an oestrous cycle-dependent mechanism controlling increased cocaine reward in females. During oestrus, ventral tegmental area (VTA) dopamine neuron activity is enhanced and drives post translational modifications at the dopamine transporter (DAT) to increase the ability of cocaine to inhibit its function, an effect mediated by estradiol. Female mice conditioned to associate cocaine with contextual cues during oestrus have enhanced mesolimbic responses to these cues in the absence of drug...
January 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28065841/the-neurotoxic-mechanisms-of-amphetamine-step-by-step-for-striatal-dopamine-depletion
#11
Che-Se Tung, Shang-Tang Chang, Chuen-Lin Huang, Nai-Kuei Huang
Amphetamine (AMPH) is a commonly abused psychostimulant that induces neuronal cell death/degeneration in humans and experimental animals. Although multiple neurotoxic mechanisms of AMPH have been intensively investigated, the interplay between these mechanisms has remained elusive. In this study, we used a rat model of AMPH-induced long-lasting striatal dopamine (DA) depletion and identified mechanisms of neurotoxicity, energy failure, excitotoxicity, and oxidative stress. Pretreatment with nicotinamide (NAM, a co-factor for the electron transport chain) blocked AMPH-induced free radical formation, energy failure, and striatal DA decrease...
January 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28063946/the-abuse-potential-of-two-novel-synthetic-cathinones-with-modification-on-the-alpha-carbon-position-2-cyclohexyl-2-methylamino-1-phenylethanone-machp-and-2-methylamino-1-phenyloctan-1-one-maop-and-their-effects-on-dopaminergic-activity
#12
Chrislean Jun Botanas, Seong Shoon Yoon, June Bryan de la Peña, Irene Joy Dela Peña, Mikyung Kim, Taeseon Woo, Joung-Wook Seo, Choon-Gon Jang, Kyung-Tae Park, Young Hun Lee, Yong Sup Lee, Hee Jin Kim, Jae Hoon Cheong
The recreational use of synthetic cathinones has dramatically increased in recent years, which is partly due to easy accessibility and ability of synthetic cathinones to exert rewarding effects similar to cocaine and methamphetamine. Many synthetic cathinones have already been scheduled in several countries; however, novel and diverse synthetic cathinones are emerging at an unprecedented rate, often outpacing regulatory processes. Recently, designer modifications of the basic cathinone molecule are usually performed on the alpha-carbon position...
January 4, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28062370/treadmill-exercise-alleviates-motor-deficits-and-improves-mitochondrial-import-machinery-in-an-mptp-induced-mouse-model-of-parkinson-s-disease
#13
Jung-Hoon Koo, Joon-Yong Cho, Ung-Bae Lee
Alpha-synuclein (α-Syn) accumulation is significantly correlated with motor deficits and mitochondrial dysfunction in Parkinson's disease (PD), but the molecular mechanism underlying its pathogenesis is unclear. In this study, we investigated the effects of treadmill exercise on motor deficits and mitochondrial dysfunction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Treadmill exercise inhibited dopaminergic neuron loss by promoting the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) and seemed to improve cell survival by reducing α-Syn expression...
January 4, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28059145/a-markov-state-based-quantitative-kinetic-model-of-sodium-release-from-the-dopamine-transporter
#14
Asghar M Razavi, George Khelashvili, Harel Weinstein
The dopamine transporter (DAT) belongs to the neurotransmitter:sodium symporter (NSS) family of membrane proteins that are responsible for reuptake of neurotransmitters from the synaptic cleft to terminate a neuronal signal and enable subsequent neurotransmitter release from the presynaptic neuron. The release of one sodium ion from the crystallographically determined sodium binding site Na2 had been identified as an initial step in the transport cycle which prepares the transporter for substrate translocation by stabilizing an inward-open conformation...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28055236/characterization-of-vntrs-within-the-entire-region-of-slc6a3-and-its-association-with-hypertension
#15
Won-Tae Kim, Se-Ra Lee, Yun-Gil Roh, Seung Il Kim, Yung Hyun Choi, Mi-Hye Mun, Mi-So Jeong, Sang Seok Koh, Sun-Hee Leem
The dopamine transporter SLC6A3 (DAT1) mediates uptake of dopamine into presynaptic terminals. In addition, in previous reports, hypertensive rats were associated with DAT gene, but the genetic association with SLC6A3 and hypertension is still unknown. We examined the distribution of variable number of tandem repeats (VNTRs) and conducted polymorphic analysis of the entire region of SLC6A3. Ten VNTR regions (MS1-10) were revealed throughout the intronic and UTRs; seven VNTR regions were newly isolated and three VNTRs were previously reported...
January 5, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28054433/insertion-of-neurotransmitters-into-lipid-bilayer-membrane-and-its-implication-on-membrane-stability-a-molecular-dynamics-study
#16
Chun Shen, Minmin Xue, Hu Qiu, Wanlin Guo
The signaling molecules in neuron called neurotransmitters play an essential role in transportation of neural signal, during which the neurotransmitters interact with not only specific receptors but also cytomembranes such as synaptic vesicle membranes and postsynaptic membranes. Here we investigate by extensive molecular dynamics simulations the atomic-scale insertion dynamics of typical neurotransmitters, including methionine enkephalin (ME), leucine enkephalin (LE), dopamine (DA), acetylcholine (ACh) and aspartic acid (ASP), into lipid bilayers...
January 5, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/28054193/personality-as-an-intermediate-phenotype-for-genetic-dissection-of-alcohol-use-disorder
#17
REVIEW
Lars Oreland, Gianvito Lagravinese, Simone Toffoletto, Kent W Nilsson, Jaanus Harro, C Robert Cloninger, Erika Comasco
Genetic and environmental interactive influences on predisposition to develop alcohol use disorder (AUD) account for the high heterogeneity among AUD patients and make research on the risk and resiliency factors complicated. Several attempts have been made to identify the genetic basis of AUD; however, only few genetic polymorphisms have consistently been associated with AUD. Intermediate phenotypes are expected to be in-between proxies of basic neuronal biological processes and nosological symptoms of AUD...
January 4, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28050877/gas-transport-properties-of-polybenzimidazole-and-poly-phenylene-oxide-mixed-matrix-membranes-incorporated-with-pda-functionalised-titanate-nanotubes
#18
V Giel, M Perchacz, J Kredatusová, Z Pientka
Functionalised titanate nanotubes (TiNTs) were incorporated to poly(5,5-bisbenzimidazole-2,2-diyl-1,3-phenylene) (PBI) or poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) for improving the interfacial compatibility between the polymer matrix and inorganic material and for altering the gas separation performance of the neat polymer membranes. Functionalisation consisted in oxidative polymerisation of dopamine-hydrochloride on the surface of non-functionalised TiNTs. Transmission electron microscopy (TEM) confirmed that a thin polydopamine (PDA) layer was created on the surface of TiNTs...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28044943/forgotten-but-not-gone-new-developments-in-the-understanding-and-treatment-of-tardive-dyskinesia
#19
Jonathan M Meyer
The broad use of atypical antipsychotics was expected to dramatically reduce the prevalence and incidence of tardive dyskinesia (TD), but data show that TD remains an important challenge due the persistent nature of its symptoms and resistance to numerous treatment modalities, including antipsychotic discontinuation. Recent insights on genetic risk factors and new concepts surrounding pathophysiology have spurred interest in the possibility of targeted treatment for TD. As will be reviewed in this article, the number of evidence-based strategies for TD treatment is small: only clonazepam, amantadine, ginkgo biloba extract, and the vesicular monoamine transporter 2 (VMAT2) inhibitor tetrabenazine have compelling data...
December 2016: CNS Spectrums
https://www.readbyqxmd.com/read/28042822/enduring-sexually-dimorphic-impact-of-in-utero-exposure-to-elevated-levels-of-glucocorticoids-on-midbrain-dopaminergic-populations
#20
REVIEW
Glenda E Gillies, Kanwar Virdee, Ilse Pienaar, Felwah Al-Zaid, Jeffrey W Dalley
Glucocorticoid hormones (GCs) released from the fetal/maternal glands during late gestation are required for normal development of mammalian organs and tissues. Accordingly, synthetic glucocorticoids have proven to be invaluable in perinatal medicine where they are widely used to accelerate fetal lung maturation when there is risk of pre-term birth and to promote infant survival. However, clinical and pre-clinical studies have demonstrated that inappropriate exposure of the developing brain to elevated levels of GCs, either as a result of clinical over-use or after stress-induced activation of the fetal/maternal adrenal cortex, is linked with significant effects on brain structure, neurological function and behaviour in later life...
December 30, 2016: Brain Sciences
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