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Ketamine schizophrenia

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https://www.readbyqxmd.com/read/29137928/camkii%C3%AE-expression-in-a-mouse-model-of-nmdar-hypofunction-schizophrenia-putative-roles-for-igf-1r-and-tlr4
#1
O M Ogundele, C C Lee
Schizophrenia (SCZ) is a neuropsychiatric disorder that is linked to social behavioral deficits and other negative symptoms associated with hippocampal synaptic dysfunction. Synaptic mechanism of schizophrenia is characterized by loss of hippocampal N-Methyl-d-Aspartate Receptor (NMDAR) activity (NMDAR hypofunction) and dendritic spines. Previous studies show that genetic deletion of hippocampal synaptic regulatory calcium-calmodulin dependent kinase II alpha (CaMKIIα) cause synaptic and behavioral defects associated with schizophrenia in mice...
November 11, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29105665/s-ketamine-induced-nmda-receptor-blockade-during-natural-speech-production-and-its-implications-for-formal-thought-disorder-in-schizophrenia-a-pharmaco-fmri-study
#2
Arne Nagels, Maurice Cabanis, Andrea Oppel, Andre Kirner-Veselinovic, Christian Schales, Tilo Kircher
Structural and functional changes in the lateral temporal language areas have been related to formal thought disorder (FTD) in schizophrenia. Continuous, natural speech production activates the right lateral temporal lobe in schizophrenia, as opposed to the left in healthy subjects. Positive and negative FTD can be elicited in healthy subjects by glutamatergic NMDA blockade with ketamine. It is unclear, whether the glutamate system is related to the reversed hemispheric lateralization during speaking in patients...
November 6, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29101022/lsd-modulates-effective-connectivity-and-neural-adaptation-mechanisms-in-an-auditory-oddball-paradigm
#3
REVIEW
Christopher Timmermann, Meg J Spriggs, Mendel Kaelen, Robert Leech, David J Nutt, Rosalyn J Moran, Robin L Carhart-Harris, Suresh D Muthukumaraswamy
Under the predictive coding framework, perceptual learning and inference are dependent on the interaction between top-down predictions and bottom-up sensory signals both between and within regions in a network. However, how such feedback and feedforward connections are modulated in the state induced by lysergic acid diethylamide (LSD) is poorly understood. In this study, an auditory oddball paradigm was presented to healthy participants (16 males, 4 female) under LSD and placebo, and brain activity was recorded using magnetoencephalography (MEG)...
October 31, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29099938/nyx-2925-is-a-novel-nmda-receptor-specific-spirocyclic-%C3%AE-lactam-that-modulates-synaptic-plasticity-processes-associated-with-learning-and-memory
#4
M Amin Khan, David R Houck, Amanda L Gross, Xiao-Lei Zhang, Cassia Cearley, Torsten M Madsen, Roger A Kroes, Patric K Stanton, Jeffrey Burgdorf, Joseph R Moskal
Background: N-methyl-D-aspartate receptors (NMDAR) are one member of a family of ionotropic glutamate receptors that play a pivotal role in synaptic plasticity processes associated with learning and have become attractive therapeutic targets for diseases such as depression, anxiety, schizophrenia, and neuropathic pain. NYX-2925 ((2S, 3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo-2,5-diazaspiro[3.4]octan-2-yl)butanamide) is one member of a spiro--lactam-based chemical platform that mimics some of the dipyrrolidine structural features of rapastinel (formerly GLYX-13: threonine-proline-proline-threonine) and is distinct from known NMDAR agonists or antagonists such as D-cycloserine, ketamine, MK-801, kynurenic acid or ifenprodil...
November 1, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29095852/neuronal-correlates-of-ketamine-and-walking-induced-gamma-oscillations-in-the-medial-prefrontal-cortex-and-mediodorsal-thalamus
#5
Katrina E Furth, Alex J McCoy, Caroline Dodge, Judith R Walters, Andres Buonanno, Claire Delaville
Alterations in the function of the medial prefrontal cortex (mPFC) and its major thalamic source of innervation, the mediodorsal (MD) thalamus, have been hypothesized to contribute to the symptoms of schizophrenia. The NMDAR antagonist ketamine, used to model schizophrenia, elicits a brain state resembling early stage schizophrenia characterized by cognitive deficits and increases in cortical low gamma (40-70 Hz) power. Here we sought to determine how ketamine differentially affects spiking and gamma local field potential (LFP) activity in the rat mPFC and MD thalamus...
2017: PloS One
https://www.readbyqxmd.com/read/29049083/ketamine-and-pharmacological-imaging-use-of-functional-magnetic-resonance-imaging-to-evaluate-mechanisms-of-action
#6
Eric A Maltbie, Gopinath S Kaundinya, Leonard L Howell
Ketamine has been used as a pharmacological model for schizophrenia as subanesthetic infusions have been shown to produce temporary schizophrenia-like symptoms in healthy humans. More recently, ketamine has emerged as a potential treatment for multiple psychiatric disorders, including treatment-resistant depression and suicidal ideation. However, the mechanisms underlying both the psychotomimetic and the therapeutic effects of ketamine remain poorly understood. This review provides an overview of what is known of the neural mechanisms underlying the effects of ketamine and details what functional MRI studies have yielded at a systems level focused on brain circuitry...
December 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29030243/the-inhibition-of-the-kynurenine-pathway-prevents-behavioral-disturbances-and-oxidative-stress-in-the-brain-of-adult-rats-subjected-to-an-animal-model-of-schizophrenia
#7
Gislaine Z Réus, Indianara R T Becker, Giselli Scaini, Fabricia Petronilho, Jean P Oses, Rima Kaddurah-Daouk, Luciane B Ceretta, Alexandra I Zugno, Felipe Dal-Pizzol, João Quevedo, Tatiana Barichello
Evidence has shown that the kynurenine pathway (KP) plays a role in the onset of oxidative stress and also in the pathophysiology of schizophrenia. The aim of this study was to use a pharmacological animal model of schizophrenia induced by ketamine to investigate if KP inhibitors could protect the brains of Wistar rats against oxidative stress and behavioral changes. Ketamine, injected at the dose of 25mg/kg, increased spontaneous locomotor activity. However, the inhibitors of tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase (IDO) and kynurenine-3-monooxygenase (KMO) were able to reverse these changes...
October 13, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28972576/the-effects-of-ketamine-on-dopaminergic-function-meta-analysis-and-review-of-the-implications-for-neuropsychiatric-disorders
#8
REVIEW
M Kokkinou, A H Ashok, O D Howes
Ketamine is a non-competitive antagonist at the N-methyl-d-aspartate receptor. It has recently been found to have antidepressant effects and is a drug of abuse, suggesting it may have dopaminergic effects. To examine the effect of ketamine on the dopamine systems, we carried out a systematic review and meta-analysis of dopamine measures in the rodent, human and primate brain following acute and chronic ketamine administration relative to a drug-free baseline or control condition. Systematic search of PubMed and PsychInfo electronic databases yielded 40 original peer-reviewed studies...
October 3, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28962045/morin-pretreatment-attenuates-schizophrenia-like-behaviors-in-experimental-animal-models
#9
Benneth Ben-Azu, Adegbuyi Oladele Aderibigbe, Itivere Adrian Omogbiya, Abayomi Mayowa Ajayi, Ezekiel O Iwalewa
Objectives Morin is a naturally occurring flavonoid with strong anti-oxidant and anti-inflammatory properties. Studies have shown that flavones modulate neurotransmission through enhancement of gamma amino butyric acid activity in the central nervous system; which led to the hypothesis that they could exert tranquilizing effects in rodents. Hence, this study was designed to evaluate the antipsychotic effect of morin on experimental animal models. Methods The antipsychotic effect of morin (25, 50 and 100 mg/kg) administered intraperitoneally (i...
September 29, 2017: Drug Research
https://www.readbyqxmd.com/read/28926001/ketamine-differential-neurophysiological-dynamics-in-functional-networks-in-the-rat-brain
#10
A Ahnaou, H Huysmans, R Biermans, N V Manyakov, W H I M Drinkenburg
Recently, the N-methyl-d-aspartate-receptor (NMDAR) antagonist ketamine has emerged as a fast-onset mechanism to achieve antidepressant activity, whereas its psychomimetic, dissociative and amnestic effects have been well documented to pharmacologically model schizophrenia features in rodents. Sleep-wake architecture, neuronal oscillations and network connectivity are key mechanisms supporting brain plasticity and cognition, which are disrupted in mood disorders such as depression and schizophrenia. In rats, we investigated the dynamic effects of acute and chronic subcutaneous administration of ketamine (2...
September 19, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28853229/average-spectral-power-changes-at-the-hippocampal-electroencephalogram-in-schizophrenia-model-induced-by-ketamine
#11
Luis Rafael L Sampaio, Lucas T N Borges, Joyse M F Silva, Francisca Roselin O de Andrade, Talita M Barbosa, Tatiane Q Oliveira, Danielle Macedo, Ricardo F Lima, Leonardo Pimentel Dantas, Manoel Cláudio Azevedo Patrocinio, Otoni C do Vale, Silvania Mendes M de Vasconcelos
The use of ketamine (Ket) as a pharmacological model of schizophrenia is an important tool for understanding the main mechanisms of glutamatergic regulated neural oscillations. Thus, the aim of the current study was to evaluate Ket induced changes in the average spectral power using the hippocampal quantitative electroencephalography (QEEG). To this end, male Wistar rats were submitted to a stereotactic surgery for the implantation of an electrode in the right hippocampus. After three days, the animals were divided into 4 groups that were treated for 10 consecutive days with Ket (10, 50 or 100 mg/kg)...
August 29, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28832723/is-forced-swimming-immobility-a-good-endpoint-for-modeling-negative-symptoms-of-schizophrenia-study-of-sub-anesthetic-ketamine-repeated-administration-effects
#12
Gilda Neves, Milene Borsoi, Camila B Antonio, Mariana A Pranke, Andresa H Betti, Stela M K Rates
Immobility time in the forced swimming has been described as analogous to emotional blunting or apathy and has been used for characterizing schizophrenia animal models. Several clinical studies support the use of NMDA receptor antagonists to model schizophrenia in rodents. Some works describe the effects of ketamine on immobility behavior but there is variability in the experimental design used leading to controversial results. In this study, we evaluated the effects of repeated administration of ketamine sub-anesthetic doses in forced swimming, locomotion in response to novelty and novel object recognition, aiming a broader evaluation of the usefulness of this experimental approach for modeling schizophrenia in mice...
July 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/28819639/antioxidant-treatment-in-male-mice-prevents-mitochondrial-and-synaptic-changes-in-an-nmda-receptor-dysfunction-model-of-schizophrenia
#13
Aarron Phensy, Christopher Driskill, Karen Lindquist, Lan Guo, Vivek Jeevakumar, Bryan Fowler, Heng Du, Sven Kroener
Glutamate theories of schizophrenia suggest that the disease is associated with a loss of NMDA receptors, specifically on GABAergic parvalbumin-expressing interneurons (PVIs), leading to changes in the excitation-inhibition balance in the prefrontal cortex (PFC). Oxidative stress contributes to the loss of PVI and the development of schizophrenia. Here, we investigated whether the glutathione precursor N-acetyl cysteine (NAC) can prevent changes in synaptic transmission at pyramidal cells and PVIs that result from developmental NMDAR blockade and how these changes are related to mitochondrial dysfunction in the PFCs of mice...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28801194/medial-septum-modulates-hippocampal-gamma-activity-and-prepulse-inhibition-in-an-n-methyl-d-aspartate-receptor-antagonist-model-of-schizophrenia
#14
L Stan Leung, Jingyi Ma
We reviewed the participation of the septohippocampal system in an animal model of schizophrenia that was acutely induced by systemic injection of an N-methyl-d-aspartate (NMDA) receptor antagonist such as phencyclidine, MK-801 and ketamine. The NMDA receptor antagonist-induced model of schizophrenia is characterized by behavioral and electrophysiological disruptions, including a decrease in prepulse inhibition of the acoustic startle response (PPI), hyperlocomotion, decrease in gating of hippocampal auditory evoked potentials and robust increase in hippocampal gamma (30-100Hz) oscillations...
August 8, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28756462/effects-of-gaba-b-receptor-positive-modulator-on-ketamine-induced-psychosis-relevant-behaviors-and-hippocampal-electrical-activity-in-freely-moving-rats
#15
Jingyi Ma, L Stan Leung
RATIONALE: Decreased GABAB receptor function is proposed to mediate some symptoms of schizophrenia. OBJECTIVES: In this study, we tested the effect of CGP7930, a GABAB receptor positive allosteric modulator, on ketamine-induced psychosis-relevant behaviors and hippocampal electrical activity in behaving rats. METHODS: Electrodes were bilaterally implanted into the hippocampus, and cannulae were placed into the lateral ventricles of Long-Evans rats...
October 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28711472/interactive-effects-of-an-n-methyl-d-aspartate-receptor-antagonist-and-a-nicotinic-acetylcholine-receptor-agonist-on-mismatch-negativity-implications-for-schizophrenia
#16
Holly K Hamilton, Deepak C D'Souza, Judith M Ford, Brian J Roach, Naomi S Kort, Kyung-Heup Ahn, Savita Bhakta, Mohini Ranganathan, Daniel H Mathalon
N-methyl-d-aspartate glutamate receptor (NMDAR) hypofunction has been implicated in the pathophysiology of schizophrenia, including auditory processing abnormalities reflected by the mismatch negativity (MMN) event-related potential component. Evidence suggesting cognitive benefits from nicotine administration, together with the high rate of cigarette use in patients with schizophrenia, has stimulated interest in whether nicotine modulates NMDAR hypofunction. We examined the interactive effects of ketamine, an NMDAR antagonist that produces transient schizophrenia-like neurophysiological effects, and nicotine, a nicotinic acetylcholine receptor (nAChR) agonist, in 30 healthy volunteers to determine whether nicotine prevents or attenuates MMN abnormalities...
July 12, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28704275/agonist-e-6837-and-antagonist-sb-271046-of-5-ht6-receptors-both-reverse-the-depressive-like-effect-induced-in-mice-by-subchronic-ketamine-administration
#17
José E Suárez-Santiago, Alfredo Briones-Aranda, Judith Espinosa-Raya, Ofir Picazo
Major depression is one of the most common affective disorders caused by schizophrenia. The administration of N-methyl-D-aspartate receptor antagonists, such as ketamine, can reproduce the negative and affective symptoms of this disorder in animals. Preclinical studies have shown that 5-HT6 receptor (5-HT6R) agonists and antagonists have a considerable antipsychotic response. The aim of the present study was to evaluate the effect of an acute treatment with an agonist, E-6837, and an antagonist, SB-271046, of 5-HT6R on the immobility induced in mice by a subchronic ketamine regimen (5 days; 10 mg/kg/day, intraperitoneal)...
July 12, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28653797/neural-correlates-of-formal-thought-disorder-an-activation-likelihood-estimation-meta-analysis
#18
Tobias Wensing, Edna C Cieslik, Veronika I Müller, Felix Hoffstaedter, Simon B Eickhoff, Thomas Nickl-Jockschat
Formal thought disorder (FTD) refers to a psychopathological dimension characterized by disorganized and incoherent speech. Whether symptoms of FTD arise from aberrant processing in language-related regions or more general cognitive networks, however, remains debated. Here, we addressed this question by a quantitative meta-analysis of published functional neuroimaging studies on FTD. The revised Activation Likelihood Estimation (ALE) algorithm was used to test for convergent aberrant activation changes in 18 studies (30 experiments) investigating FTD, of which 17 studies comprised schizophrenia patients and one study healthy subjects administered to S-ketamine...
October 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28634445/antioxidant-treatment-with-n-acetyl-cysteine-prevents-the-development-of-cognitive-and-social-behavioral-deficits-that-result-from-perinatal-ketamine-treatment
#19
Aarron Phensy, Hasmik E Duzdabanian, Samantha Brewer, Anurag Panjabi, Christopher Driskill, Annuska Berz, George Peng, Sven Kroener
Alterations of the normal redox state can be found in all stages of schizophrenia, suggesting a key role for oxidative stress in the etiology and maintenance of the disease. Pharmacological blockade of N-methyl-D-aspartic acid (NMDA) receptors can disrupt natural antioxidant defense systems and induce schizophrenia-like behaviors in animals and healthy human subjects. Perinatal administration of the NMDA receptor (NMDAR) antagonist ketamine produces persistent behavioral deficits in adult mice which mimic a range of positive, negative, and cognitive symptoms that characterize schizophrenia...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28634108/disturbances-of-novel-object-exploration-and-recognition-in-a-chronic-ketamine-mouse-model-of-schizophrenia
#20
Maria Jelena Hauser, Dirk Isbrandt, Jochen Roeper
Schizophrenia is a chronic and devastating disease with an overall lifetime risk of 1%. While positive symptoms of schizophrenia such as hallucinations and delusions are reduced by antipsychotic medication based on the inhibition of type 2 dopaminergic receptors (D2R), negative symptoms (e.g. reduced motivation) and cognitive symptoms (e.g. impaired working memory) of schizophrenia are not effectively treated by current medication. This dichotomy might arise in part because of our limited understanding of the pathophysiology of negative and cognitive symptoms in schizophrenia...
June 17, 2017: Behavioural Brain Research
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