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https://www.readbyqxmd.com/read/28430979/effect-of-physical-exercise-and-acute-escitalopram-on-the-excitability-of-brain-monoamine-neurons-in-vivo-electrophysiological-study-in-rats
#1
Eliyahu Dremencov, Kristína Csatlósová, Barbora Durišová, Lucia Lapínová, Lubica Lacinová, Daniela Ježová
Background: The antidepressant effect of physical exercise has been reported in several clinical and animal studies. Since serotonin (5-HT), norepinephrine and dopamine play a central role in depression, it is possible that the beneficial effects of physical exercise are mediated via monoamine pathways. This study investigates the effects of voluntary wheel running (VWR) on the excitability of monoamine neurons. Material and methods: Male Sprague-Dawley rats were used in the study...
April 18, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28428755/pharmacological-analysis-of-the-anti-epileptic-mechanisms-of-fenfluramine-in-scn1a-mutant-zebrafish
#2
Jo Sourbron, Ilse Smolders, Peter de Witte, Lieven Lagae
Dravet syndrome (DS) is a genetic encephalopathy that is characterized by severe seizures and prominent co-morbidities (e.g., physical, intellectual disabilities). More than 85% of the DS patients carry an SCN1A mutation (sodium channel, voltage gated, type I alpha subunit). Although numerous anti-epileptic drugs have entered the market since 1990, these drugs often fail to adequately control seizures in DS patients. Nonetheless, current clinical data shows significant seizure reduction in DS patients treated with the serotonergic (5-hydroxytryptamine, 5-HT) drug fenfluramine (FA)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28427888/dopamine-elevates-intracellular-zinc-concentration-in-cultured-rat-embryonic-cortical-neurons-through-the-camp-nitric-oxide-signaling-cascade
#3
Hui-Hsing Hung, Lung-Sen Kao, Pei-Shan Liu, Chien-Chang Huang, De-Ming Yang, Chien-Yuan Pan
Zinc ion (Zn(2+)), the second most abundant transition metal after iron in the body, is essential for neuronal activity and also induces toxicity if the concentration is abnormally high. Our previous results show that exposure of cultured cortical neurons to dopamine elevates intracellular Zn(2+) concentrations ([Zn(2+)]i) and induces autophagosome formation but the mechanism is not clear. In this study, we characterized the signaling pathway responsible for the dopamine-induced elevation of [Zn(2+)]i and the effect of [Zn(2+)]i in modulating the autophagy in cultured rat embryonic cortical neurons...
April 17, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28425631/restraint-stress-increases-prolactin-mediated-phosphorylation-of-signal-transducer-and-activator-of-transcription-5-in-the-hypothalamus-and-adrenal-cortex-in-the-male-mouse
#4
S E Kirk, T Y Xie, F J Steyn, D R Grattan, S J Bunn
Prolactin is a pleiotropic peptide hormone produced by the lactotrophs in the anterior pituitary. Its rate of secretion is primarily regulated by a negative feedback mechanism whereby prolactin stimulates the activity of the tuberoinfundibular dopaminergic (TIDA) neurons, increasing their release of dopamine which accesses the pituitary via the median eminence to suppress further prolactin secretion. In addition to its well established role in lactation, circulating prolactin is secreted in response to stress, although the mechanism by which this is achieved or its cellular targets are unknown...
April 20, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28420875/down-regulation-of-cholinergic-signaling-in-the-habenula-induces-anhedonia-like-behavior
#5
Seungrie Han, Soo Hyun Yang, Jin Yong Kim, Seojung Mo, Esther Yang, Ki Myung Song, Byung-Joo Ham, Naguib Mechawar, Gustavo Turecki, Hyun Woo Lee, Hyun Kim
Dysfunction of cholinergic signaling in the brain has long been believed to be associated with depressive disorders. However, the functional impact of habenular cholinergic signaling on the specified depressive behaviors is not well understood. Here, we demonstrated that the expression levels of cholinergic signaling genes (CHAT, VACHT, CHT, CHRNA3, CHRNB3 and CHRNB4) were down-regulated in a chronic restraint stress (CRS) rat model of depression, in which rats display depression-like behaviors such as anhedonia and mood despair...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28419642/nicotine-induced-molecular-alterations-are-modulated-by-gabab-receptor-activity
#6
Andres P Varani, Valeria T Pedrón, Amira J Aon, Christian Höcht, Gabriela B Acosta, Bernhard Bettler, Graciela N Balerio
It has been demonstrated that GABAB receptors modulate nicotine (NIC) reward effect; nevertheless, the mechanism implicated is not well known. In this regard, we evaluated the involvement of GABAB receptors on the behavioral, neurochemical, biochemical and molecular alterations associated with the rewarding effects induced by NIC in mice, from a pharmacological and genetic approach. NIC-induced rewarding properties (0.5 mg/kg, subcutaneously, sc) were evaluated by conditioned place preference (CPP) paradigm...
April 17, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28416594/new-repeat-polymorphism-in-the-akt1-gene-predicts-striatal-dopamine-d2-d3-receptor-availability-and-stimulant-induced-dopamine-release-in-the-healthy-human-brain
#7
Elena Shumay, Corinde E Wiers, Ehsan Shokri-Kojori, Sung Won Kim, Colin A Hodgkinson, Hui Sun, Dardo Tomasi, Christopher T Wong, Daniel R Weinberger, Gene-Jack Wang, Joanna S Fowler, Nora D Volkow
The role of the protein kinase Akt1 in dopamine neurotransmission is well recognized and has been implicated in schizophrenia and psychosis. However, the extent to which variants in the AKT1 gene influence dopamine neurotransmission is not well understood.Here we investigated the effect of a newly characterized variant number tandem repeat (VNTR) polymorphism in AKT1 (major alleles: L- (8 repeats) and H- (9 repeats)) on striatal dopamine D2/D3 receptor (DRD2) availability and on dopamine release in healthy volunteers...
April 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28414692/neuronal-fibers-and-neurotransmitter-receptor-expression-in-the-human-endolymphatic-sac
#8
Martin Nue Møller, Svend Kirkeby, Jonas Vikeså, Finn Cilius Nielsen, Per Cayé-Thomasen
INTRODUCTION: Recent studies suggest that the human endolymphatic sac (ES) may have multiple functions, including an ion-transport capacity comparable to the kidney, an immunological capacity and a possible natriuretic capacity. Further, there have been speculations of a yet undefined role in intracranial pressure homeostasis. The anatomical location towards the sigmoid sinus would suggest a possible endo- and/or paracrine signaling. However, neuronal connections may also apply, but it remains very scarcely explored in the human ES...
April 14, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28412910/aripiprazole-a-drug-that-displays-partial-agonism-and-functional-selectivity
#9
Erin W Tuplin, Matthew R Holahan
The treatment of schizophrenia is challenging due to the wide range of symptoms (positive, negative, cognitive) associated with the disease. Typical antipsychotics that antagonize D2 receptors are effective in treating positive symptoms, but extrapyramidal side-effects (EPS) are a common occurrence. Atypical antipsychotics targeting 5-TH2A and D2 receptors are more effective at treating cognitive and negative symptoms compared to typical antipsychotics, but these drugs also result in side-effects such as metabolic syndromes...
April 13, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28409931/1-4-18-f-fluorobenzyl-4-tetrahydrofuran-2-yl-methyl-piperazine-a-novel-suitable-radioligand-with-low-lipophilicity-for-imaging-sigma-1-receptors-in-the-brain
#10
Yingfang He, Fang Xie, Jiajun Ye, Winnie Deuther-Conrad, Bixiao Cui, Liang Wang, Jie Lu, Jörg Steinbach, Peter Brust, Yiyun Huang, Jie Lu, Hongmei Jia
We have designed and synthesized novel piperazine compounds with low lipophilicity as σ1 receptor ligands. 1-(4-Fluorobenzyl)-4-((tetrahydrofuran-2-yl)methyl)piperazine (10) possessed low nanomolar σ1 receptor affinity and high selectivity toward the vesicular acetylcholine transporter (>2000-fold), σ2 receptors (52-fold), adenosine A2A, adrenergic α2, cannabinoid CB1, dopamine D1, D2L, γ-aminobutyric acid A (GABAA), NMDA, melatonin MT1, MT2 and serotonin 5-HT1 receptors. The corresponding radiotracer [(18)F]10 demonstrated high brain uptake and extremely high brain-to-blood ratios in biodistribution studies in mice...
April 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28405133/risperidone-induced-adverse-drug-reactions-and-role-of-drd2-141-c-ins-del-and-5htr2c-759-c-t-genetic-polymorphisms-in-patients-with-schizophrenia
#11
Charanraj Goud Alladi, Anbarasan Mohan, Deepak Gopal Shewade, Ravi Philip Rajkumar, Surendiran Adithan, Karthick Subramanian
OBJECTIVE: To determine the adverse drug reaction (ADR) profile of risperidone and their association with dopamine (DRD2 - 141 C Ins/Del/rs1799732) and serotonin receptor (5HTR2C -759 C>T/rs3813929) gene polymorphisms in patients with schizophrenia. MATERIALS AND METHODS: The study was conducted among 289 patients who were diagnosed with schizophrenia and were on treatment with risperidone (4-8 mg/day)-based therapy for a minimum of 4 weeks. Genotyping was carried by real-time quantitative polymerase chain reaction...
January 2017: Journal of Pharmacology & Pharmacotherapeutics
https://www.readbyqxmd.com/read/28404690/pharmacologic-characterization-of-valbenazine-nbi-98854-and-its-metabolites
#12
Dimitri E Grigoriadis, Evan Smith, Sam R J Hoare, Ajay Madan, Haig Bozigian
The vesicular monoamine transporter 2 (VMAT2) is an integral presynaptic protein that regulates the packaging and subsequent release of dopamine and other monoamines from neuronal vesicles into the synapse. Valbenazine (NBI-98854), a novel compound that selectively inhibits VMAT2, is being developed for the treatment of tardive dyskinesia. Valbenazine is converted to two significant circulating metabolites in vivo, namely, (+)-α-dihydrotetrabenazine (R,R,R-DHTBZ) and a mono-oxy metabolite, NBI-136110. Radioligand binding studies were conducted to assess and compare valbenazine, tetrabenazine and their respective metabolites in their abilities to selectively and potently inhibit [(3)H]-DHTBZ binding to VMAT2 in rat striatal, rat forebrain, and human platelet homogenates...
April 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28396142/atypical-binding-at-dopamine-and-serotonin-transporters-contribute-to-the-discriminative-stimulus-effects-of-mephedrone
#13
Alyssa F DeLarge, Laura L Erwin, Peter J Winsauer
Mephedrone (4-methylmethcathinone), a constituent of the recreational substances known as "bath salts", is a synthetic cathinone that can produce auditory and visual hallucinations, as well as problematic cardiovascular effects. This study compared the discriminative stimulus effects of mephedrone (0.32-10 mg/kg) with other prototypical drugs of abuse: cocaine (0.56-32 mg/kg), d-amphetamine (0.18-3.2 mg/kg), ketamine (1.8-18 mg/kg), phencyclidine (PCP, 1-5.6 mg/kg), heroin (1-10 mg/kg), 2,5-dimethoxy-4-iodoamphetamine (R-DOI, 0...
April 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28391970/novel-5-ht7r-antagonists-arylsulfonamide-derivatives-of-aryloxy-propyl-piperidines-add-on-effect-to-the-antidepressant-activity-of-ssri-and-dri-and-pro-cognitive-profile
#14
Vittorio Canale, Anna Partyka, Rafał Kurczab, Martyna Krawczyk, Tomasz Kos, Grzegorz Satała, Bartłomiej Kubica, Magdalena Jastrzębska-Więsek, Anna Wesołowska, Andrzej J Bojarski, Piotr Popik, Paweł Zajdel
A novel series of arylsulfonamide derivatives of (aryloxy)propyl piperidines was designed to obtain potent 5-HT7R antagonists. Among the compounds evaluated herein, 3-chloro-N-{1-[3-(1,1-biphenyl-2-yloxy)2-hydroxypropyl]piperidin-4-yl}benzenesulfonamide (25) exhibited antagonistic properties at 5-HT7R and showed selectivity over selected serotoninergic and dopaminergic receptors, as well as over serotonin, noradrenaline and dopamine transporters. Compound 25 demonstrated significant antidepressant-like activity in the forced swim test (0...
May 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28390892/opposite-control-of-mesocortical-and-mesoaccumbal-dopamine-pathways-by-serotonin2b-receptor-blockade-involvement-of-medial-prefrontal-cortex-serotonin1a-receptors
#15
Céline Devroye, Nasser Haddjeri, Adeline Cathala, Renaud Rovera, Filippo Drago, Pier Vincenzo Piazza, Francesc Artigas, Umberto Spampinato
Recent studies have shown that serotonin2B receptor (5-HT2BR) antagonists exert opposite facilitatory and inhibitory effects on dopamine (DA) release in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc), respectively, thereby leading to the proposal that these compounds could provide an interesting pharmacological tool for treating schizophrenia. Although the mechanisms underlying these effects remain unknown, several data in the literature suggest that 5-HT1ARs located into the mPFC could participate in this interaction...
April 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28388095/biomimetic-bacterial-identification-platform-based-on-thermal-wave-transport-analysis-twta-through-surface-imprinted-polymers
#16
Erik Steen Redeker, Kasper Eersels, Onno Akkermans, Jeroen Royakkers, Simba Dyson, Kunya Nurekeyeva, Beniamino Ferrando, Peter Cornelis, Marloes Peeters, Patrick Wagner, Hanne Diliën, Bart van Grinsven, Thomas Jan Cleij
This paper introduces a novel bacterial identification assay based on thermal wave analysis through surface-imprinted polymers (SIPs). Aluminum chips are coated with SIPs, serving as synthetic cell receptors that have been combined previously with the heat-transfer method (HTM) for the selective detection of bacteria. In this work, the concept of bacterial identification is extended toward the detection of nine different bacterial species. In addition, a novel sensing approach, thermal wave transport analysis (TWTA), is introduced, which analyzes the propagation of a thermal wave through a functional interface...
April 11, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28387682/exendin-4-treatment-improves-lps-induced-depressive-like-behavior-without-affecting-pro-inflammatory-cytokines
#17
Filip Ventorp, Cecilie Bay-Richter, Analise Sauro Nagendra, Shorena Janelidze, Viktor Sjödahl Matsson, Jack Lipton, Ulrika Nordström, Åsa Westrin, Patrik Brundin, Lena Brundin
BACKGROUND: Exendin-4 is a peptide agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently in clinical trials as a potential disease-modifying therapy for Parkinson's disease. In light of this, it is important to understand potential modes of action of exendin-4 in the brain. Exendin-4 is neuroprotective and has been proposed to be directly anti-inflammatory, and that this is one way it reduces neurodegeneration. However, prior studies have focused on animal models involving both neurodegeneration and inflammation, therefore, it is also possible that the observed decreased inflammation is secondary to reduced neurodegeneration...
April 4, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28386699/dreamlike-effects-of-lsd-on-waking-imagery-in-humans-depend-on-serotonin-2a-receptor-activation
#18
Rainer Kraehenmann, Dan Pokorny, Leonie Vollenweider, Katrin H Preller, Thomas Pokorny, Erich Seifritz, Franz X Vollenweider
RATIONALE: Accumulating evidence indicates that the mixed serotonin and dopamine receptor agonist lysergic acid diethylamide (LSD) induces an altered state of consciousness that resembles dreaming. OBJECTIVES: This study aimed to test the hypotheses that LSD produces dreamlike waking imagery and that this imagery depends on 5-HT2A receptor activation and is related to subjective drug effects. METHODS: Twenty-five healthy subjects performed an audiorecorded guided mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally)...
April 7, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28384481/cognitive-states-influence-dopamine-driven-aberrant-learning-in-parkinson-s-disease
#19
James F Cavanagh, Andrea A Mueller, Darin R Brown, Jacqueline R Janowich, Jacqueline H Story-Remer, Ashley Wegele, Sarah Pirio Richardson
Individual differences in dopaminergic tone underlie tendencies to learn from reward versus punishment. These effects are well documented in Parkinson's patients, who vacillate between low and high tonic dopaminergic states as a function of medication. Yet very few studies have investigated the influence of higher-level cognitive states known to affect downstream dopaminergic learning in Parkinson's patients. A dopamine-dependent cognitive influence over learning would provide a candidate mechanism for declining cognitive integrity and motivation in Parkinson's patients...
March 20, 2017: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/28376679/dopamine-and-%C3%AE-opioid-receptor-dysregulation-in-the-brains-of-binge-eating-female-rats-possible-relevance-in-the-psychopathology-and-treatment-of-binge-eating-disorder
#20
David J Heal, Michelle Hallam, Michael Prow, Jane Gosden, Sharon Cheetham, Yong K Choi, Frank Tarazi, Peter Hutson
Adult, female rats given irregular, limited access to chocolate develop binge-eating behaviour with normal bodyweight and compulsive/perseverative and impulsive behaviours similar to those in binge-eating disorder. We investigated whether (a) dysregulated central nervous system dopaminergic and opioidergic systems are part of the psychopathology of binge-eating and (b) these neurotransmitter systems may mediate the actions of drugs ameliorating binge-eating disorder psychopathology. Binge-eating produced a 39% reduction of striatal D1 receptors with 22% and 23% reductions in medial and lateral caudate putamen and a 22% increase of striatal μ-opioid receptors...
April 1, 2017: Journal of Psychopharmacology
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