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Ketamine schizophrenia

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https://www.readbyqxmd.com/read/29338491/the-effect-of-ketamine-on-the-consolidation-and-extinction-of-contextual-fear-memory
#1
Nicholas E Clifton, Kerrie L Thomas, Jeremy Hall
Ketamine, principally an antagonist of N-methyl-ᴅ-aspartate receptors, induces schizophrenia-like symptoms in adult humans, warranting its use in the investigation of psychosis-related phenotypes in animal models. Genomic studies further implicate N-methyl-ᴅ-aspartate receptor-mediated processes in schizophrenia pathology, together with more broadly-defined synaptic plasticity and associative learning processes. Strong pathophysiological links have been demonstrated between fear learning and psychiatric disorders such as schizophrenia...
January 1, 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29337238/advantages-of-the-alpha-lipoic-acid-association-with-chlorpromazine-in-a-model-of-schizophrenia-induced-by-ketamine-in-rats-behavioral-and-oxidative-stress-evidences
#2
Luis Rafael Leite Sampaio, Francisco Maurício Sales Cysne Filho, Jamily Cunha de Almeida, Danilo Dos Santos Diniz, Cláudio Felipe Vasconcelos Patrocínio, Caren Nádia Soares de Sousa, Manoel Cláudio Azevedo Patrocínio, Danielle S Macêdo, Silvânia Maria Mendes Vasconcelos
Schizophrenia is a chronic mental disorder reported to compromise about 1% of the world's population. Although its pathophysiological process is not completely elucidated, evidence showing the presence of an oxidative imbalance has been increasingly highlighted in the literature. Thus, the use of antioxidant substances may be of importance for schizophrenia treatment. The objective of this study was to evaluate the behavioral and oxidative alterations by the combination of chlorpromazine (CP) and alpha-lipoic acid (ALA), a potent antioxidant, in the ketamine (KET) model of schizophrenia in rats...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29330003/effects-of-5-ht5a-receptor-blockade-on-amnesia-or-forgetting
#3
L Aparicio-Nava, L A Márquez-García, A Meneses
Previously the effects (0.01-3.0 mg/kg) of post-training SB-699551 (a 5-HT5A receptor antagonist) were reported in the associative learning task of autoshaping, showing that SB-699551 (0.1 mg/kg) decreased lever-press conditioned responses (CR) during short-term (STM; 1.5-h) or (3.0 mg/kg) long-term memory (LTM; 24-h); relative to the vehicle animals. Moreover, as pro-cognitive efficacy of SB-699551 was reported in the ketamine-model of schizophrenia. Hence, firstly aiming improving performance (conditioned response, CR), in this work autoshaping lever-press vs...
January 9, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29313138/do-psychoactive-drugs-have-a-therapeutic-role-in-compulsivity-studies-on-schedule-induced-polydipsia
#4
Elena Martín-González, Ángeles Prados-Pardo, Santiago Mora, Pilar Flores, Margarita Moreno
RATIONALE: Clinical studies have shown that some psychoactive recreational drugs have therapeutic applications in anxiety, depression, and schizophrenia. However, to date, there are few studies on the therapeutic potential efficacy of recreational drugs in compulsive neuropsychiatric disorders. OBJECTIVES: We explored the therapeutic potential of different psychoactive and psychedelic drugs in a preclinical model of compulsive behavior. METHODS: Outbred male Wistar rats were selected as either high (HD) or low (LD) drinkers according to their behavior in schedule-induced polydipsia (SIP)...
January 8, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29247465/cannabinoid-glutamate-interactions-and-neural-oscillations-implications-for-psychosis
#5
Mohamed A Sherif, Jose A Cortes-Briones, Mohini Ranganathan, Patrick D Skosnik
Preclinical and clinical data suggest that the cannabinoid and glutamatergic systems are implicated in the pathophysiology of schizophrenia (SZ), the prototypical psychotic disorder. This has led to distinct "cannabis" and "ketamine" models of SZ, respectively. However, these two models need not be mutually exclusive. Indeed, in several brain regions implicated in the putative neural circuitry of SZ (e.g., hippocampus, frontal cortex, cerebellum), cannabinoid receptors type 1 (CB1Rs) and glutamate N-methyl-D-aspartate receptors (NMDARs) have direct and indirect interactions...
December 15, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29236648/a-putative-electrophysiological-biomarker-of-auditory-sensory-memory-encoding-is-sensitive-to-pharmacological-alterations-of-excitatory-inhibitory-balance-in-male-macaque-monkeys
#6
William B Holliday, Kate Gurnsey, Robert A Sweet, Tobias Teichert
BACKGROUND: The amplitude of the auditory evoked N1 component that can be derived from noninvasive electroencephalographic recordings increases as a function of time between subsequent tones. N1 amplitudes in individuals with schizophrenia saturate at a lower asymptote, thus giving rise to a reduced dynamic range. Reduced N1 dynamic range is a putative electrophysiological biomarker of altered sensory memory function in individuals with the disease. To date, it is not clear what determines N1 dynamic range and what causes reduced N1 dynamic range in individuals with schizophrenia...
December 13, 2017: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/29196183/nmda-receptor-antagonist-rodent-models-for-cognition-in-schizophrenia-and-identification-of-novel-drug-treatments-an-update
#7
REVIEW
Daniela Cadinu, Ben Grayson, Giovanni Podda, Michael K Harte, Nazanin Doostdar, Joanna C Neill
Negative and cognitive deficit symptoms in schizophrenia remain an unmet clinical need. Improved understanding of the neuro- and psychopathology of cognitive dysfunction in the illness is urgently required to enhance the development of new improved therapeutic strategies. Careful validation of animal models that mimic the behaviour and pathology of complex psychiatric disorders is an essential step towards this goal. Non-competitive NMDAR (N-Methyl-d-aspartate receptor) antagonists e.g. phencyclidine (PCP), ketamine and dizocilpine (MK-801) can effectively replicate certain aspects of negative and cognitive deficits associated with schizophrenia in animals...
November 28, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29171010/prenatal-exposure-to-ketamine-in-rats-implications-on-animal-models-of-schizophrenia
#8
Carlos M Coronel-Oliveros, Renny Pacheco-Calderón
Schizophrenia is a complex neuropsychiatric disorder characterized by hallucinations, delusions, anhedonia, flat affect and cognitive impairments. The aim of this study was to propose a prenatal treatment with ketamine, a psychedelic drug that acts as a non-competitive inhibitor of glutamate NMDA receptors, as a neurodevelopmental animal model of schizophrenia. The drug was applied (i.m. 60 mg.kg(-1)  h(-1) ) in pregnant Sprague-Dawley rats on gestational Day 14. Offspring behavior was studied on pubertal (4 weeks old) and adult (10 weeks old) stages...
November 24, 2017: Developmental Psychobiology
https://www.readbyqxmd.com/read/29167877/utility-of-imaging-based-biomarkers-for-glutamate-targeted-drug-development-in-psychotic-disorders-a-randomized-clinical-trial
#9
Daniel C Javitt, Cameron S Carter, John H Krystal, Joshua T Kantrowitz, Ragy R Girgis, Lawrence S Kegeles, John D Ragland, Richard J Maddock, Tyler A Lesh, Costin Tanase, Philip R Corlett, Douglas L Rothman, Graeme Mason, Maolin Qiu, James Robinson, William Z Potter, Marlene Carlson, Melanie M Wall, Tse-Hwei Choo, Jack Grinband, Jeffrey A Lieberman
Importance: Despite strong theoretical rationale and preclinical evidence, several glutamate-targeted treatments for schizophrenia have failed in recent pivotal trials, prompting questions as to target validity, compound inadequacy, or lack of target engagement. A key limitation for glutamate-based treatment development is the lack of functional target-engagement biomarkers for translation between preclinical and early-stage clinical studies. We evaluated the utility of 3 potential biomarkers-ketamine-evoked changes in the functional magnetic imaging (fMRI) blood oxygen level-dependent response (pharmacoBOLD), glutamate proton magnetic resonance spectroscopy (1H MRS), and task-based fMRI-for detecting ketamine-related alterations in brain glutamate...
November 22, 2017: JAMA Psychiatry
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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