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https://www.readbyqxmd.com/read/28645061/the-neurochemical-consequences-of-methamphetamine-self-administration-in-male-and-female-rats
#1
Andrew Johansen, Lisa M McFadden
BACKGROUND: Methamphetamine (METH) is an addictive substance that is used in both males and females. Few preclinical studies have focused on understanding sex-differences in the neurochemical consequences of contingent METH. The purpose of the current study was to investigate potential sex-differences in the neurochemical consequences of METH self-administration. METHODS: Male and female adult rats were given extended access to METH or saline self-administration for 7d...
June 6, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28644892/r-modafinil-exerts-weak-effects-on-spatial-memory-acquisition-and-dentate-gyrus-synaptic-plasticity
#2
Bharanidharan Shanmugasundaram, Yogesh D Aher, Jana Aradska, Marija Ilic, Daniel Daba Feyissa, Predrag Kalaba, Nilima Y Aher, Vladimir Dragacevic, Babak Saber Marouf, Thierry Langer, Harald H Sitte, Harald Hoeger, Gert Lubec, Volker Korz
Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO) is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gyrus long-term potentiation (DG-LTP). Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO) or saline were administered for three days during the hole-board test and in in vivo DG-LTP. Synaptic levels of dopamine receptors D1R, D2R, dopamine transporter (DAT), and its phosphorylated form (ph-DAT) in DG tissue 4 h after LTP induction were quantified by western blot analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28631404/structural-connectivity-differences-in-motor-network-between-tremor-dominant-and-nontremor-parkinson-s-disease
#3
Gaetano Barbagallo, Maria Eugenia Caligiuri, Gennarina Arabia, Andrea Cherubini, Angela Lupo, Rita Nisticò, Maria Salsone, Fabiana Novellino, Maurizio Morelli, Giuseppe Lucio Cascini, Domenico Galea, Aldo Quattrone
Motor phenotypes of Parkinson's disease (PD) are recognized to have different prognosis and therapeutic response, but the neural basis for this clinical heterogeneity remains largely unknown. The main aim of this study was to compare differences in structural connectivity metrics of the main motor network between tremor-dominant and nontremor PD phenotypes (TD-PD and NT-PD, respectively) using probabilistic tractography-based network analysis. A total of 63 PD patients (35 TD-PD patients and 28 NT-PD patients) and 30 healthy controls underwent a 3 T MRI...
June 20, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28625719/atypical-dopamine-transporter-inhibitors-r-modafinil-and-jhw-007-differentially-affect-d2-autoreceptor-neurotransmission-and-the-firing-rate-of-midbrain-dopamine-neurons
#4
Alicia J Avelar, J Cao, Amy Hauck Newman, Michael J Beckstead
Abuse of psychostimulants like cocaine that inhibit dopamine (DA) reuptake through the dopamine transporter (DAT) represents a major public health issue, however FDA-approved pharmacotherapies have yet to be developed. Recently a class of ligands termed "atypical DAT inhibitors" has gained attention due to their range of effectiveness in increasing extracellular dopamine (DA) levels without demonstrating significant abuse liability. These compounds not only hold promise as therapeutic agents to treat stimulant use disorders but also as experimental tools to improve our understanding of DAT function...
June 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28623359/allosteric-modulatory-effects-of-sri-20041-and-sri-30827-on-cocaine-and-hiv-1-tat-protein-binding-to-human-dopamine-transporter
#5
Wei-Lun Sun, Pamela M Quizon, Yaxia Yuan, Wei Zhang, Subramaniam Ananthan, Chang-Guo Zhan, Jun Zhu
Dopamine transporter (DAT) is the target of cocaine and HIV-1 transactivator of transcription (Tat) protein. Identifying allosteric modulatory molecules with potential attenuation of cocaine and Tat binding to DAT are of great scientific and clinical interest. We demonstrated that tyrosine 470 and 88 act as functional recognition residues in human DAT (hDAT) for Tat-induced inhibition of DA transport and transporter conformational transitions. Here we investigated the allosteric modulatory effects of two allosteric ligands, SRI-20041 and SRI-30827 on cocaine binding on wild type (WT) hDAT, Y470 H and Y88 F mutants...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28601527/spatial-distortion-related-to-time-compression-during-spatiotemporal-production-in-parkinson-s-disease
#6
Motoyasu Honma, Yuki Murai, Shuhei Shima, Yuko Yotsumoto, Takeshi Kuroda, Akinori Futamura, Azusa Shiromaru, Ikuya Murakami, Mitsuru Kawamura
To produce coordinated manual actions within specific space and time, their relationship must be properly dealt with in a sensorimotor system. This study examined how such a coordination system might be impaired in normal aging and in Parkinson's disease (PD). Using a tablet device, young participants, elderly participants, and patients with PD were tested for concurrent production of distance and duration as well as single production of distance or duration alone. Results were analyzed in relation to deficiency of presynaptic dopamine transporter (DaT) in the striatum...
June 7, 2017: Neuropsychologia
https://www.readbyqxmd.com/read/28598964/changes-in-expression-of-dopamine-its-receptor-and-transporter-in-nucleus-accumbens-of-heroin-addicted-rats-with-brain-derived-neurotrophic-factor-bdnf-overexpression
#7
Yixin Li, Baijuan Xia, Rongrong Li, Dan Yin, Wenmei Liang
BACKGROUND The aim of this study was to explore how changes in the expression of BDNF in MLDS change the effect of BDNF on dopamine (DA) neurons, which may have therapeutic implications for heroin addiction. MATERIAL AND METHODS We established a rat model of heroin addiction and observed changes in the expression of BDNF, DA, dopamine receptor (DRD), dopamine transporter (DAT), and other relevant pathways in NAc. We also assessed the effect of BDNF overexpression in the NAc, behavioral changes of heroin-conditioned place preference (CPP), and naloxone withdrawal in rats with high levels of BDNF...
June 9, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28597409/progression-and-persistence-of-neurotoxicity-induced-by-mdma-in-dopaminergic-regions-of-the-mouse-brain-and-association-with-noradrenergic-gabaergic-and-serotonergic-damage
#8
Giulia Costa, Micaela Morelli, Nicola Simola
The amphetamine-related drug 3,4-methylenedioxymethamphetamine (MDMA) is known to induce neurotoxic damage in dopaminergic regions of the mouse brain. In order to characterize how the number of administrations influenced the severity of MDMA-induced dopaminergic damage and to describe the localization and persistence of this damage, we evaluated the changes in tyrosine hydroxylase (TH) and dopamine transporter (DAT) in different regions of the mouse brain. Moreover, we investigated whether dopaminergic damage was associated with noradrenergic, GABAergic, and serotonergic damage, by evaluating the changes in noradrenaline transporter (NET), glutamic acid decarboxylase-67 (GAD-67), and serotonin transporter (SERT)...
June 9, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28595287/conversion-to-parkinson-disease-in-the-pars-hyposmic-and-dopamine-transporter-deficit-prodromal-cohort
#9
Danna Jennings, Andrew Siderowf, Matthew Stern, John Seibyl, Shirley Eberly, David Oakes, Kenneth Marek
Importance: Detecting individuals at risk for Parkinson disease (PD) during the prodromal phase could clarify disease mechanisms and allow for treatment earlier in the disease process to possibly slow or prevent the onset of motor PD. Objective: To determine if the combination of smell identification testing followed by dopamine transporter (DAT) imaging can accurately and efficiently identify individuals from the general population at risk for conversion to a clinical diagnosis of PD...
June 8, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28594540/noradrenergic-modulation-of-dopamine-transmission-evoked-by-electrical-stimulation-of-the-locus-coeruleus-in-the-rat-brain
#10
Jin W Park, Rohan V Bhimani, Jinwoo Park
Central norepinephrine (NE) and dopamine (DA) are involved in a variety of physiological functions and behaviors. Accumulating evidence suggests that NE neurons originating from the locus coeruleus (LC) innervate DA neurons of the ventral tegmental area (VTA) and influence VTA-DA neural activity. However, the underlying mechanisms of how LC-NE regulates DA transmission via VTA-DA neurons remain largely unexplored. Herein, we investigated how electrical stimulation of the LC modulates VTA-DA neurotransmission in the nucleus accumbens (NAc)...
June 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28588873/a-72-year-old-with-eyelid-opening-apraxia-in-steele-richardson-olszewski-syndrome
#11
Ihtesham A Qureshi, Mohtashim A Qureshi, Alberto Maud
In our patient with Steele-Richardson-Olszewski syndrome presenting with apraxia of eyelid opening, there is a possibility to be readily confused with conditions presenting in similar pattern such as blepharospasm and eyelid ptosis. Therefore, it is essential to correlate the clinical findings with electromyographic recordings and dopamine transporter scan (DaT).
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28582390/polymorphisms-in-dopaminergic-system-genes-association-with-criminal-behavior-and-self-reported-aggression-in-violent-prison-inmates-from-pakistan
#12
Muhammad Imran Qadeer, Ali Amar, J John Mann, Shahida Hasnain
Genetic factors contribute to antisocial and criminal behavior. Dopamine transporter DAT-1 (SLC6A3) and DRD2 gene for the dopamine-2 receptor are dopaminergic system genes that regulate dopamine reuptake and signaling, and may be part of the pathogenesis of psychiatric disorders including antisocial behaviors and traits. No previous studies have analyzed DAT-1 and DRD2 polymorphisms in convicted murderers, particularly from Indian subcontinent. In this study we investigated the association of 40 bp VNTR polymorphism of DAT-1 and Taq1 variant of DRD2 gene (rs1800479) with criminal behavior and self-reported aggression in 729 subjects, including 370 men in Pakistani prisons convicted of first degree murder(s) and 359 control men without any history of violence or criminal tendency...
2017: PloS One
https://www.readbyqxmd.com/read/28579325/a-peptide-disrupting-the-d2r-dat-interaction-protects-against-dopamine-neurotoxicity
#13
Ping Su, Fang Liu
Dopamine reuptake from extracellular space to cytosol leads to accumulation of dopamine, which triggers neurotoxicity in dopaminergic neurons. Previous studies have shown that both dopamine D2 receptor (D2R) and dopamine transporter (DAT) are involved in dopamine neurotoxicity. However, blockade of either D2R or DAT causes side effects due to antagonism of other physiological functions of these two proteins. We previously found that DAT can form a protein complex with D2R and its cell surface expression is facilitated via D2R-DAT interaction, which regulates dopamine reuptake and intracellular dopamine levels...
June 1, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28571709/phospho-specific-antibodies-targeting-the-amino-terminus-of-the-human-dopamine-transporter
#14
Caline S Karam, Namita Sen, Jonathan A Javitch
The dopamine transporter (DAT), which mediates the inactivation of released dopamine through its reuptake, is the primary molecular target for the actions of psychostimulants. An increasing number of studies support an essential role for phosphorylation of serines (Ser) in the distal amino (N) terminus of DAT in regulating its function. Still, the molecular details of the regulation of phosphorylation and its impact on function are not fully understood. To address this, we have developed and characterized two distinct phospho-antibodies that recognize human DAT when it is phosphorylated at Ser7 or Ser12...
May 30, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28557437/differentiating-physicochemical-properties-between-addictive-and-nonaddictive-adhd-drugs-revealed-by-molecular-dynamics-simulation-studies
#15
Panpan Wang, Xiaoyu Zhang, Tingting Fu, Shuang Li, Bo Li, Weiwei Xue, Xiaojun Yao, Yuzong Chen, Feng Zhu
Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed mental disorder of children and adolescents. Although psychostimulants are currently the first-line drugs for ADHD, their highly addictive profile raises great abuse concerns. It is known that psychostimulants' addictiveness is largely attributed to their interaction with dopamine transporter (DAT) and their binding modes in DAT can thus facilitate the understanding of the mechanism underlining drugs' addictiveness. However, no DAT residue able to discriminate ADHD drugs' addictiveness is identified, and the way how different drug structures affect their abuse liability is still elusive...
June 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28548869/neurotransmitter-receptor-availability-in-the-rat-brain-is-constant-in-a-24-hour-period
#16
A Oskamp, F Wedekind, T Kroll, D Elmenhorst, A Bauer
Wakefulness and sleep are fundamental characteristics of the brain. We, therefore, hypothesized that transmitter systems contribute to their regulation and will exhibit circadian alterations. We assessed the concentration of various neurotransmitter receptors and transporters including adenosinergic (A1AR, A2AAR, and ENT1), dopaminergic (D1R, D2R, and DAT), and serotonergic (5-HT2AR) target proteins. Adult male Sprague Dawley rats were used and maintained in a 12 h light: 12 h dark cycle (lights on from 07:00 h to 19:00 h)...
May 26, 2017: Chronobiology International
https://www.readbyqxmd.com/read/28530234/n-alkylated-analogs-of-4-methylamphetamine-4-ma-differentially-affect-monoamine-transporters-and-abuse-liability
#17
Ernesto Solis, John S Partilla, Farhana Sakloth, Iwona Ruchala, Kathryn L Schwienteck, Louis J De Felice, Jose M Eltit, Richard A Glennon, S Stevens Negus, Michael H Baumann
Clandestine chemists synthesize novel stimulant drugs by exploiting structural templates known to target monoamine transporters for dopamine, norepinephrine and serotonin (DAT, NET, and SERT, respectively). 4-Methylamphetamine (4-MA) is an emerging drug of abuse that interacts with transporters, but limited structure-activity data are available for its analogs. Here we employed uptake and release assays in rat brain synaptosomes, voltage-clamp current measurements in cells expressing transporters, and calcium flux assays in cells co-expressing transporters and calcium channels to study the effects of increasing N-alkyl chain length of 4-MA on interactions at DAT, NET and SERT...
May 22, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28520803/multiple-modality-biomarker-prediction-of-cognitive-impairment-in-prospectively-followed-de-novo-parkinson-disease
#18
Chelsea Caspell-Garcia, Tanya Simuni, Duygu Tosun-Turgut, I-Wei Wu, Yu Zhang, Mike Nalls, Andrew Singleton, Leslie A Shaw, Ju-Hee Kang, John Q Trojanowski, Andrew Siderowf, Christopher Coffey, Shirley Lasch, Dag Aarsland, David Burn, Lana M Chahine, Alberto J Espay, Eric D Foster, Keith A Hawkins, Irene Litvan, Irene Richard, Daniel Weintraub
OBJECTIVES: To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments. METHODS: We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition...
2017: PloS One
https://www.readbyqxmd.com/read/28511263/diagnosis-and-treatment-of-functional-psychogenic-parkinsonism
#19
Kathrin LaFaver, Alberto J Espay
Functional (psychogenic) parkinsonism (FP) is recognized by the mandatory combination of marked slowness without progressive decrement on repetitive manual tasks and variable resistance against passive movements in the absence of cogwheel rigidity. Other functional phenotypes, such as functional tremor and functional gait impairment, may coexist. Although neither necessary nor sufficient for the diagnosis of FP, supportive historical clues include the sudden onset of symptoms and absent or nonphysiologic response to levodopa...
April 2017: Seminars in Neurology
https://www.readbyqxmd.com/read/28506818/measuring-inhibition-of-monoamine-reuptake-transporters-by-new-psychoactive-substances-nps-in-real-time-using-a-high-throughput-fluorescence-based-assay
#20
Anne Zwartsen, Anouk H A Verboven, Regina G D M van Kleef, Fiona M J Wijnolts, Remco H S Westerink, Laura Hondebrink
The prevalence and use of new psychoactive substances (NPS) is increasing and currently over 600 NPS exist. Many illicit drugs and NPS increase brain monoamine levels by inhibition and/or reversal of monoamine reuptake transporters (DAT, NET and SERT). This is often investigated using labor-intensive, radiometric endpoint measurements. We investigated the applicability of a novel and innovative assay that is based on a fluorescent monoamine mimicking substrate. DAT, NET or SERT-expressing human embryonic kidney (HEK293) cells were exposed to common drugs (cocaine, dl-amphetamine or MDMA), NPS (4-fluoroamphetamine, PMMA, α-PVP, 5-APB, 2C-B, 25B-NBOMe, 25I-NBOMe or methoxetamine) or the antidepressant fluoxetine...
May 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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