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https://www.readbyqxmd.com/read/29343767/blockade-of-trpv1-inhibits-methamphetamine-induced-rewarding-effects
#1
Yu-Hua Tian, Shi-Xun Ma, Kwang-Wook Lee, Sunmee Wee, George F Koob, Seok-Yong Lee, Choon-Gon Jang
Methamphetamine (MAP) is the most widely used psychostimulant in the world, but the exact mechanisms underlying MAP addiction are not yet fully understood. Recent studies have identified the distribution of TRPV1 in several brain regions that are related to drug addiction, including nucleus accumbens (NAc) and dorsal striatum (DSt). In the present study, we performed conditioned place preference (CPP) and self-administration tests to examine the effects of capsazepine (CPZ) and SB366791 (SB) on MAP reward. We found that both CPZ and SB significantly inhibited MAP-induced CPP and self-administration; in contrast, TRPV1 knock-out (KO) mice did not develop MAP-induced CPP...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339668/proinflammatory-cytokines-and-oxidative-stress-decrease-the-transport-of-dopamine-precursor-tyrosine-in-human-fibroblasts
#2
Ravi Vumma, Jessica Johansson, Nikolaos Venizelos
BACKGROUND: Proinflammatory cytokines and oxidative stress responses have been extensively implicated in the pathophysiology of neuropsychiatric disorders over the past 2 decades. Moreover, disturbed transport of the dopamine precursor (i.e., the amino acid tyrosine) has been demonstrated, in different studies, across fibroblast cell membranes obtained from neuropsychiatric patients. However, the role and influences of proinflammatory cytokines and oxidative stress, and the reasons for disturbed tyrosine transport in neuropsychiatric disorders, are still not evaluated...
January 16, 2018: Neuropsychobiology
https://www.readbyqxmd.com/read/29337309/role-for-vglut2-in-selective-vulnerability-of-midbrain-dopamine-neurons
#3
Thomas Steinkellner, Vivien Zell, Zachary J Farino, Mark S Sonders, Michael Villeneuve, Robin J Freyberg, Serge Przedborski, Wei Lu, Zachary Freyberg, Thomas S Hnasko
Parkinson's disease is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area are more resistant to this degeneration than those in the SNc, though the mechanisms for selective resistance or vulnerability remain poorly understood. A key to elucidating these processes may lie within the subset of DA neurons that corelease glutamate and express the vesicular glutamate transporter VGLUT2. Here, we addressed the potential relationship between VGLUT expression and DA neuronal vulnerability by overexpressing VGLUT in DA neurons of flies and mice...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337277/compensatory-dopaminergic-cholinergic-interactions-in-conflict-processing-evidence-from-patients-with-parkinson-s-disease
#4
REVIEW
Kamin Kim, Nicolaas I Bohnen, Martijn L T M Müller, Cindy Lustig
Executive functions are complex both in the cognitive operations involved and in the neural structures and functions that support those operations. This complexity makes executive function highly vulnerable to the detrimental effects of aging, brain injury, and disease, but may also open paths to compensation. Neural compensation is often used to explain findings of additional or altered patterns of brain activations by older adults or patient populations compared to young adults or healthy controls, especially when associated with relatively preserved performance...
January 11, 2018: NeuroImage
https://www.readbyqxmd.com/read/29334320/human-dopamine-transporter-the-first-implementation-of-a-combined-in-silico-in-vitro-approach-revealing-the-substrate-and-inhibitor-specificities
#5
Teodora Djikic, Yasmina Martí, Francesca Spyrakis, Thorsten Lau, Paolo Benedetti, Gavin Davey, Patrick Schloss, Kemal Yelekci
Parkinson's disease (PD) is characterized by the loss of dopamine-generating neurons in the substantia nigra (SN) and corpus striatum (CS). Current treatments alleviate PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons. New drugs targeting the dopaminergic neurons by specific uptake through the human dopamine transporter (hDAT) could represent a viable strategy for establishing selective neuroprotection. Molecules able to increase the bioactive amount of extracellular dopamine (DA), thereby enhancing and compensating a loss of dopaminergic neurotransmission, and to exert neuroprotective response because of their accumulation in the cytoplasm, are required...
January 15, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29332198/drug-delivery-and-transport-into-the-central-circulation-an-example-of-zero-order-in-vivo-absorption-of-rotigotine-from-a-transdermal-patch-formulation
#6
Willi Cawello, Marina Braun, Jens-Otto Andreas
BACKGROUND AND OBJECTIVE: Pharmacokinetic studies using deconvolution methods and non-compartmental analysis to model clinical absorption of drugs are not well represented in the literature. The purpose of this research was (1) to define the system of equations for description of rotigotine (a dopamine receptor agonist delivered via a transdermal patch) absorption based on a pharmacokinetic model and (2) to describe the kinetics of rotigotine disposition after single and multiple dosing...
January 13, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29329781/dopamine-transporter-trafficking-is-regulated-by-neutral-sphingomyelinase-2-ceramide-kinase
#7
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
#8
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/29317605/non-invasive-modulation-reduces-repetitive-behavior-in-a-rat-model-through-the-sensorimotor-cortico-striatal-circuit
#9
Henriette Edemann-Callesen, Bettina Habelt, Franziska Wieske, Mark Jackson, Niranjan Khadka, Daniele Mattei, Nadine Bernhardt, Andreas Heinz, David Liebetanz, Marom Bikson, Frank Padberg, Ravit Hadar, Michael A Nitsche, Christine Winter
Involuntary movements as seen in repetitive disorders such as Tourette Syndrome (TS) results from cortical hyperexcitability that arise due to striato-thalamo-cortical circuit (STC) imbalance. Transcranial direct current stimulation (tDCS) is a stimulation procedure that changes cortical excitability, yet its relevance in repetitive disorders such as TS remains largely unexplored. Here, we employed the dopamine transporter-overexpressing (DAT-tg) rat model to investigate behavioral and neurobiological effects of frontal tDCS...
January 10, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29302200/reexamination-of-dopaminergic-amacrine-cells-in-the-rabbit-retina-confocal-analysis-with-double-and-triple-labeling-immunohistochemistry
#10
Jong Woo Lee, Min Young Lim, Yong Soo Park, Su Jin Park, In-Beom Kim
Dopaminergic amacrine cells (DACs) are among the most well-characterized neurons in the mammalian retina, and their connections to AII amacrine cells have been described in detail. However, the stratification of DAC dendrites differs based on their location in the inner plexiform layer (IPL), raising the question of whether all AII lobules are modulated by dopamine release from DACs. The present study aimed to clarify the relationship between DACs and AII amacrine cells, and to further elucidate the role of dopamine at synapses with AII amacrine cell...
December 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/29299388/individual-differences-in-eeg-correlates-of-recognition-memory-due-to-dat-polymorphisms
#11
Paolo Medrano, Erika Nyhus, Andrew Smolen, Tim Curran, Robert S Ross
Introduction: Although previous research suggests that genetic variation in dopaminergic genes may affect recognition memory, the role dopamine transporter expression may have on the behavioral and EEG correlates of recognition memory has not been well established. Objectives: The study aims to reveal how individual differences in dopaminergic functioning due to genetic variations in the dopamine transporter gene influences behavioral and EEG correlates of recognition memory...
December 2017: Brain and Behavior
https://www.readbyqxmd.com/read/29295587/dopamine-and-levodopa-prodrugs-for-the-treatment-of-parkinson-s-disease
#12
REVIEW
Fatma Haddad, Maryam Sawalha, Yahya Khawaja, Anas Najjar, Rafik Karaman
Background: Parkinson's disease is an aggressive and progressive neurodegenerative disorder that depletes dopamine (DA) in the central nervous system. Dopamine replacement therapy, mainly through actual dopamine and its original prodrug l-dopa (LD), faces many challenges such as poor blood brain barrier penetration and decreased response to therapy with time. Methods: The prodrugs described herein are ester, amide, dimeric amide, carrier-mediated, peptide transport-mediated, cyclic, chemical delivery systems and enzyme-models prodrugs designed and made by chemical means, and their bioavailability was studied in animals...
December 25, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29290055/variability-of-presynaptic-nigrostriatal-dopaminergic-function-and-clinical-heterogeneity-in-a-dopa-responsive-dystonia-family-with-gch-1-gene-mutation
#13
Juei-Jueng Lin, Chin-Song Lu, Chon-Haw Tsai
We studied the presynaptic nigrostriatal dopaminergic function using single photon emission computed tomography (SPECT) imaging of a 99mTc-TRODAT-1 (TRODAT) scan in a dopa-responsive dystonia (DRD) family with the guanosine triphosphate cyclohydrolase 1 (GCH-1) gene mutation. Clinically, there was presentation of intrafamilial variability in the DRD family. The index patient was a 10-year-old girl with classic DRD and normal presynaptic nigrostriatal dopaminergic function. However, her grandmother, a 79-year-old woman, presented with slowly progressive Parkinson's disease (PD) without dystonic symptoms and excellent response to dopaminergic therapy for 21 years...
December 30, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/29289701/dopamine-transporter-knockdown-mice-in-the-behavioral-pattern-monitor-a-robust-reproducible-model-for-mania-relevant-behaviors
#14
Molly A Kwiatkowski, Gerhard Hellemann, Catherine A Sugar, Zackary A Cope, Arpi Minassian, William Perry, Mark A Geyer, Jared W Young
Efforts to replicate results from both basic and clinical models have highlighted problems with reproducibility in science. In psychiatry, reproducibility issues are compounded because the complex behavioral syndromes make many disorders challenging to model. We develop translatable tasks that quantitatively measure psychiatry-relevant behaviors across species. The behavioral pattern monitor (BPM) was designed to analyze exploratory behaviors, which are altered in patients with bipolar disorder (BD), especially during mania episodes...
December 28, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29288796/dha-mitigates-autistic-behaviors-accompanied-by-dopaminergic-change-in-a-gene-prenatal-stress-mouse-model
#15
Fumihiro Matsui, Patrick Hecht, Kanji Yoshimoto, Yoshihisa Watanabe, Masafumi Morimoto, Kevin Fritsche, Matthew Will, David Beversdorf
Autism Spectrum Disorder (ASD) is characterized by impairments in social interaction, social communication, and repetitive and stereotyped behaviors. Recent work has begun to explore gene x environmental interactions in the etiology of ASD. We previously reported that prenatal stress exposure in stress-susceptible heterozygous serotonin transporter (SERT) KO pregnant dams in a mouse model resulted in autism-like behavior in the offspring (SERT/S mice). The association between prenatal stress and ASD appears to be affected by maternal SERT genotype in clinical populations as well...
December 27, 2017: Neuroscience
https://www.readbyqxmd.com/read/29288746/a-new-synthetic-drug-5-2-aminopropyl-indole-5-it-induces-rewarding-effects-and-increases-dopamine-d1-receptor-and-dopamine-transporter-mrna-levels
#16
Chrislean Jun Botanas, Seong Shoon Yoon, June Bryan de la Peña, Irene Joy Dela Peña, Mikyung Kim, Raly James Custodio, Taeseon Woo, Joung-Wook Seo, Choon-Gon Jang, Ji Seul Yang, Yoon Mi Yoon, Yong Sup Lee, Hee Jin Kim, Jae Hoon Cheong
In recent years, there has been a marked increase in the use of recreational synthetic psychoactive substances, which is a cause of concern among healthcare providers and legal authorities. In particular, there have been reports on the misuse of 5-(2-aminopropyl)indole (5-API; 5-IT), a new synthetic drug, and of fatal and non-fatal intoxication. Despite these reports, little is known about its psychopharmacological effects and abuse potential. Here, we investigated the abuse potential of 5-IT by evaluating its rewarding and reinforcing effects through conditioned place preference (CPP) (1, 10, and 30 mg/kg, i...
December 27, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29281965/is-dopamine-transporter-mediated-dopaminergic-signaling-in-the-retina-a-noninvasive-biomarker-for-attention-deficit-hyperactivity-disorder-a-study-in-a-novel-dopamine-transporter-variant-val559-transgenic-mouse-model
#17
Heng Dai, Chad R Jackson, Gwynne L Davis, Randy D Blakely, Douglas G McMahon
BACKGROUND: Dopamine (DA) is a critical neuromodulator in the retina. Disruption of retinal DA synthesis and signaling significantly attenuates light-adapted, electroretinogram (ERG) responses, as well as contrast sensitivity and acuity. As these measures can be detected noninvasively, they may provide opportunities to detect disease processes linked to perturbed DA signaling. Recently, we identified a rare, functional DA transporter (DAT, SLC6A3) coding substitution, Ala559Val, in subjects with attention-deficit/hyperactivity disorder (ADHD), demonstrating that DAT Val559 imparts anomalous DA efflux (ADE) with attendant physiological, pharmacological, and behavioral phenotypes...
December 28, 2017: Journal of Neurodevelopmental Disorders
https://www.readbyqxmd.com/read/29281030/motor-learning-and-metaplasticity-in-striatal-neurons-relevance-for-parkinson-s-disease
#18
Nadia Giordano, Attilio Iemolo, Maria Mancini, Fabrizio Cacace, Maria De Risi, Emanuele Claudio Latagliata, Veronica Ghiglieri, Gian Carlo Bellenchi, Stefano Puglisi-Allegra, Paolo Calabresi, Barbara Picconi, Elvira De Leonibus
Nigro-striatal dopamine transmission is central to a wide range of neuronal functions, including skill learning, which is disrupted in several pathologies such as Parkinson's disease. The synaptic plasticity mechanisms, by which initial motor learning is stored for long time periods in striatal neurons, to then be gradually optimized upon subsequent training, remain unexplored. Addressing this issue is crucial to identify the synaptic and molecular mechanisms involved in striatal-dependent learning impairment in Parkinson's disease...
December 21, 2017: Brain: a Journal of Neurology
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
#19
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/29273699/false-positive-dopamine-transporter-imaging-due-to-therapeutic-dextroamphetamine-amphetamine
#20
Joseph Frankl, Sudeshna Bose, Phillip H Kuo
Dopamine transporter (DAT) single-photon emission computed tomography (SPECT) is an accurate adjunct to clinical evaluation for Parkinson's disease (PD) in cases where the diagnosis is difficult. Dopaminergic medications may significantly impact DAT availability and thus uptake of DAT tracers. A patient had a false-positive DAT-SPECT while on dextroamphetamine/amphetamine for attention deficit/hyperactivity disorder. DAT-SPECT normalized after withholding amphetamine therapy. This report demonstrates that an accurate medication history combined with the knowledge of drugs that interfere with DAT imaging is critical to ensure accuracy...
December 22, 2017: Journal of Nuclear Medicine Technology
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