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NMDA antagonist

Mariola Herbet, Aleksandra Szopa, Sylwia Wośko, Anna Serefko, Magdalena Izdebska, Monika Gawrońska-Grzywacz, Iwona Piątkowska-Chmiel, Martyna Janas, Renata Gieroba, Agnieszka Korga, Ewa Poleszak, Jarosław Dudka
BACKGROUND: Depressive disorders are associated with oxidative stress. Therefore, it is interesting if antidepressants can affect redox equilibrium and signaling. The first step of our study was to determine the influence of the adenosine system on the antidepressant-like activity of non-competitive antagonist of the NMDA receptor complex - dizocilpine (MK-801). To this aim, two behavioral tests commonly used to assess the antidepressant capability of drugs - the forced swim test (FST) and tail suspension test (TST), were performed...
October 10, 2016: CNS & Neurological Disorders Drug Targets
Mark Galizio, Brooke April, Melissa Deal, Andrew Hawkey, Danielle Panoz-Brown, Ashley Prichard, Katherine Bruce
The Odor Span Task is an incrementing non-matching-to-sample procedure that permits the study of behavior under the control of multiple stimuli. Rats are exposed to a series of odor stimuli and selection of new stimuli is reinforced. Successful performance thus requires remembering which stimuli have previously been presented during a given session. This procedure has been frequently used in neurobiological studies as a rodent model of working memory; however, only a few studies have examined the effects of drugs on performance in this task...
October 17, 2016: Journal of the Experimental Analysis of Behavior
Erik Nylander, Alfhild Grönbladh, Sofia Zelleroth, Shanti Diwakarla, Fred Nyberg, Mathias Hallberg
Human growth hormone (GH) displays promising protective effects in the central nervous system after damage caused by various insults. Current evidence suggests that these effects may involve N-methyl-D-aspartate (NMDA) receptor function, a receptor that also is believed to play a role in opioid-induced neurotoxicity. The aims of the present study were to examine the acute toxic effects of methadone, an opioid receptor agonist and NMDA receptor antagonist, as well as to evaluate the protective properties of recombinant human GH (rhGH) on methadone-induced toxicity...
October 13, 2016: Neuroscience
Jatin Machhi, Navnit Prajapati, Ashutosh Tripathi, Zalak S Parikh, Ashish M Kanhed, Kirti Patel, Prakash P Pillai, Rajani Giridhar, Mange Ram Yadav
Excitotoxicty, a key pathogenic event is characteristic of the onset and development of neurodegeneration. The glutamatergic neurotransmission mediated through different glutamate receptor subtypes plays a pivotal role in the onset of excitotoxicity. The role of NMDA receptor (NMDAR), a glutamate receptor subtype, has been well established in the excitotoxicity pathogenesis. NMDAR overactivation triggers excessive calcium influx resulting in excitotoxic neuronal cell death. In the present study, a series of benzazepine derivatives, with the core structure of 3-methyltetrahydro-3H-benzazepin-2-one, were synthesised in our laboratory and their NMDAR antagonist activity was determined against NMDA-induced excitotoxicity using SH-SY5Y cells...
October 15, 2016: Molecular Neurobiology
Bandhan Mukherjee, Qi Yuan
The interactions of L-type calcium channels (LTCCs) and NMDA receptors (NMDARs) in memories are poorly understood. Here we investigated the specific roles of anterior piriform cortex (aPC) LTCCs and NMDARs in early odor preference memory in mice. Using calcium imaging in aPC slices, LTCC activation was shown to be dependent on NMDAR activation. Either D-APV (NMDAR antagonist) or nifedipine (LTCC antagonist) reduced somatic calcium transients in pyramidal cells evoked by lateral olfactory tract stimulation. However, nifedipine did not further reduce calcium in the presence of D-APV...
October 14, 2016: Scientific Reports
Majid Motaghinejad, Manijeh Motevalian, Behnaz Shabab
Neurodegeneration induced by methylphenidate (MPH), as a central stimulant with unknown long-term consequences, in adult rats' brain and the possible mechanisms involved were studied. Rats were acutely treated with MPH in presence and absence of some receptor antagonists such as ketamine, topiramate, yohimibine and haloperidol. Motor activity and anxiety level in rats were monitored. Anti-oxidant and inflammatory parameters were also measured in isolated hippocampus and cerebral cortex. MPH treated groups (10 and 20 mg/kg) demonstrated anxiety-like behavior and increased motor activity...
October 14, 2016: Fundamental & Clinical Pharmacology
Maria Jenelyn M Alviar, Tom Hale, Monalisa Dungca
BACKGROUND: This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable, and disabling. Various medications have been studied in the treatment of phantom pain. There is currently uncertainty in the optimal pharmacologic management of PLP. OBJECTIVES: This review aimed to summarise the evidence of effectiveness of pharmacologic interventions in treating PLP...
October 14, 2016: Cochrane Database of Systematic Reviews
Walid A Alsharafi, Bo Xiao, Jing Li
OBJECTIVES: Regulation of N-methyl-d-aspartate (NMDA) subunits NR2A and NR2B expression during status epilepticus (SE) remains incompletely understood. Here we explored the role of brain-enriched microRNA (miR)-139-5p in this process. METHODS: miRNA microarray was performed to examine changes in miRNA expression in the rat pilocarpine model following NMDA-receptor blockade. The dynamic expression patterns of miR-139-5p, NR2A, and NR2B levels were measured in rats during the three phases of temporal lobe epilepsy (TLE) development using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot...
October 12, 2016: Epilepsia
Sara de la Salle, Joelle Choueiry, Dhrasti Shah, Hayley Bowers, Judy McIntosh, Vadim Ilivitsky, Verner Knott
N-methyl-D-aspartate (NMDA) receptor antagonists administered to healthy humans results in schizophrenia-like symptoms, which preclinical research suggests are due to glutamatergically altered brain oscillations. Here, we examined resting-state electroencephalographic activity in 21 healthy volunteers assessed in a placebo-controlled, double-blind, randomized study involving administration of either a saline infusion or a sub-anesthetic dose of ketamine, an NMDA receptor antagonist. Frequency-specific current source density (CSD) was assessed at sensor-level and source-level using eLORETA within regions of interest of a triple network model of schizophrenia (this model posits a dysfunctional switching between large-scale Default Mode and Central Executive networks by the monitor-controlling Salience Network)...
2016: Frontiers in Pharmacology
Elzbieta Zieminska, Jacek Lenart, Dominik Diamandakis, Jerzy W Lazarewicz
Using primary cultures of rat cerebellar granule cells (CGC) we examined the role of calcium transients induced by tetrabromobisphenol A (TBBPA) in triggering oxidative stress and cytotoxicity. CGC were exposed for 30 min to 10 or 25 µM TBBPA. Changes in intracellular calcium concentration ([Ca(2+)]i), in the production of reactive oxygen species (ROS), and in the potential of mitochondria (∆Ψm) were measured fluorometrically during the exposure. The intracellular glutathione (GSH) and catalase activity were determined after the incubation; cell viability was evaluated 24 h later...
October 7, 2016: Neurochemical Research
Luiz Luciano Falconi-Sobrinho, Tayllon Dos Anjos-Garcia, Daoud Hibrahim Elias Filho, Norberto Cysne Coimbra
The medial prefrontal cortex can influence unconditioned fear-induced defensive mechanisms organised by diencephalic neurons that are under tonic GABAergic inhibition. The posterior hypothalamus (PH) is involved with anxiety- and panic attack-like responses. To understand this cortical mediation, our study characterised anterior cingulate cortex (ACC)-PH pathways and investigated the effect of ACC local inactivation with lidocaine. We also investigated the involvement of PH ionotropic glutamate receptors in the defensive behaviours and fear-induced antinociception by microinjecting NBQX (an AMPA/kainate receptor antagonist) and LY235959 (a NMDA receptor antagonist) into the PH...
October 3, 2016: Neuropharmacology
Keith L Shelton
Inhalants are a loosely organized category of abused compounds defined entirely by their common route of administration. Inhalants include volatile solvents, fuels, volatile anesthetics, gasses, and liquefied refrigerants, among others. They are ubiquitous in modern society as ingredients in a wide variety of household, commercial, and medical products. Persons of all ages abuse inhalants but the highest prevalence of abuse is in younger adolescents. Although inhalants have been shown to act upon a host of neurotransmitter receptors, the stimulus effects of the few inhalants which have been trained or tested in drug discrimination procedures suggest that their discriminative stimulus properties are mediated by a few key neurotransmitter receptor systems...
October 7, 2016: Current Topics in Behavioral Neurosciences
Sudarat Nimitvilai, Chang You, Devinder S Arora, Maureen A McElvain, Bertha J Vandegrift, Mark S Brodie, John J Woodward
Drugs of abuse increase the activity of dopaminergic neurons of the ventral tegmental area (VTA), and output from the VTA is critical for both natural and drug-induced reward and reinforcement. Ethanol and the abused inhalant toluene both enhance VTA neuronal firing, but the mechanisms of this effect is not fully known. In this study, we used extracellular recordings to compare the actions of toluene and ethanol on DA VTA neurons. Both ethanol and toluene increased the firing rate of DA neurons, although toluene was ~100 times more potent than ethanol...
2016: Frontiers in Neuroscience
Trina Sengupta, Ashok Kumar Jaryal, Hruda Nanda Mallick
Glutamate when microinjected at the medial preoptic area (mPOA) influences brain temperature (Tbr) and body temperature (Tb) in rats. Glutamate and its various receptors are present at the mPOA. The aim of this study was to identify the contribution of each of the ionotropic glutamatergic receptors at the mPOA on changes in Tbr and Tb in freely moving rats. Adult male Wistar rats (n=40) were implanted with bilateral guide cannula with indwelling styli above the mPOA. A telemetric transmitter was implanted at the peritoneum to record Tb and locomotor activity (LMA)...
October 2016: Journal of Thermal Biology
Elizabeth Finbarrs-Bello, Emmanuel Nebeuwa Obikili, Esom Emmanuel Anayochukwu, Anyanwu Emeka Godson
AIM: This study evaluated the curative potential of Crinum giganteum in the treatment of schizophrenia using an NMDA-receptor antagonist-induced schizophrenic Wistar rat model. METHODS: Twenty-five adult Wistar rats of both sexes of average weights 180 g were divided into two groups: control and schizophrenic rat models. The controls received 0.1 ml of 0. 9% saline, while schizophrenia was induced in models using 25 mg/kg of ketamine hydrochloride (i.p.) for 7 days...
September 15, 2016: Open Access Macedonian Journal of Medical Sciences
Peivand Ghasemzadeh, Seyed Mahdi Rezayat, Sharareh Adeli, Nahid Rahbar-Roshandel
We investigated the effects of 25Mg-Porphyrin-Fullerene nanoparticles, (25MgPMC16) smart ferroporphyrin nanoparticles, on PC12 cells exposed to oxygen-glucose deprivation/reperfusion. In order to explore its effect on cells under oxygen-glucose deprivation conditions, the cultures were pretreated with 25MgPMC16 24 hours prior to oxygen-glucose deprivation/reperfusion. To initiate the oxygen-glucose deprivation/reperfusion, the cell culture medium was replaced with a glucose-free medium and the cells were transferred to a humidified incubation chamber in a mixture of 95% N2 and 5% CO2 at 37° C for 30, 60 and 120 min...
August 2016: Acta Medica Iranica
Courtney C Cocilova, Sarah L Milton
Harmful algal blooms are increasing in frequency and extent worldwide and occur nearly annually off the west coast of Florida where they affect both humans and wildlife. The dinoflagellate Karenia brevis is a key organism in Florida red tides that produces a suite of potent neurotoxins collectively referred to as the brevetoxins (PbTx). Brevetoxins bind to and open voltage gated sodium channels (VGSC), increasing cell permeability in excitable cells and depolarizing nerve and muscle tissue. Exposed animals may thus show muscular and neurological symptoms including head bobbing, muscle twitching, paralysis, and coma; large HABs can result in significant morbidity and mortality of marine life, including fish, birds, marine mammals, and sea turtles...
September 28, 2016: Aquatic Toxicology
Tatiane da Silva Araújo, Adriano Jose Maia Chaves Filho, Aline Santos Monte, Ana Isabelle de Góis Queiroz, Rafaela Carneiro Cordeiro, Michel de Jesus Souza Machado, Ricardo de Freitas Lima, David Freitas de Lucena, Michael Maes, Danielle Macêdo
Immune dysregulation observed in schizophrenia alters tryptophan metabolism. Tryptophan metabolism is triggered by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Tryptophan is converted to quinolinic acid, a potent neurotoxin, and to kynurenic acid, an NMDA antagonist. 1-Methyl-D-tryptophan (MDT) inhibits IDO. Melatonin is metabolized by IDO while inhibiting TDO. We evaluated the reversal of ketamine-induced schizophrenia-like behavioral and neurochemical alterations in mice by the administration of MDT (20 or 40 mg/kg, i...
September 21, 2016: Journal of Psychiatric Research
Rong Hu, Juan Chen, Brendan Lujan, Ruixue Lei, Mi Zhang, Zefen Wang, Mingxia Liao, Zhiqiang Li, Yu Wan, Fang Liu, Hua Feng, Qi Wan
Ionotropic activation of NMDA receptors (NMDARs) requires agonist glutamate and co-agonist glycine. Here we show that glycine enhances the activation of cell survival-promoting kinase Akt in cultured cortical neurons in which both the channel activity of NMDARs and the glycine receptors are pre-inhibited. The effect of glycine is reduced by shRNA-mediated knockdown of GluN2A subunit-containing NMDARs (GluN2ARs), suggesting that a non-ionotropic activity of GluN2ARs mediates glycine-induced Akt activation. In support of this finding, glycine enhances Akt activation in HEK293 cells over-expressing GluN2ARs...
October 3, 2016: Scientific Reports
Silvana Lopes-Azevedo, Cristiane Busnardo, Fernando Morgan Aguiar Corrêa
Previously, we reported that microinjection of l-proline (l-Pro) into the paraventricular nucleus of the hypothalamus (PVN) caused vasopressin-mediated pressor responses in unanesthetized rats. In the present study, we report on the central mechanisms involved in the mediation of the cardiovascular effects caused by the microinjection of l-Pro into the PVN. Microinjection of increasing doses of l-Pro (3-100 nmol/100nL) into the PVN caused dose-related pressor and bradycardic responses. No cardiovascular responses were observed after the microinjection of equimolar doses (33nmol/100nL) of its isomer d-Proline (d-Pro) or Mannitol...
September 29, 2016: Brain Research
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