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Ketamine schizophrenia

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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
#1
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
#2
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
https://www.readbyqxmd.com/read/28634087/treatment-with-levetiracetam-improves-cognition-in-a-ketamine-rat-model-of-schizophrenia
#3
Ming Teng Koh, Yi Shao, Sharon Rosenzweig-Lipson, Michela Gallagher
Imbalance in neural excitation and inhibition is associated with behavioral dysfunction in individuals with schizophrenia and at risk for this illness. We examined whether targeting increased neural activity with the antiepileptic agent, levetiracetam, would benefit memory performance in a preclinical model of schizophrenia that has been shown to exhibit hyperactivity in the hippocampus. Adult rats exposed to ketamine subchronically during late adolescence showed impaired hippocampal-dependent memory performance...
June 17, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28612134/ketamine-induced-behavioural-and-brain-oxidative-changes-in-mice-an-assessment-of-possible-beneficial-effects-of-zinc-as-mono-or-adjunct-therapy
#4
Olakunle James Onaolapo, Olayemi Quyyom Ademakinwa, Temitayo Opeyemi Olalekan, Adejoke Yetunde Onaolapo
RATIONALE: We studied the influence of zinc, haloperidol or olanzapine on neurobehaviour (open-field, radial arm maze and elevated plus maze) and brain antioxidant status in vehicle- or ketamine-treated mice, with the aim of ascertaining the potentials of zinc in counteracting ketamine's effects. OBJECTIVES: Experiment 1 assessed the effects of zinc in healthy animals and the relative degrees of modulation of ketamine's effects by zinc, haloperidol or olanzapine, respectively...
June 14, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28579941/chronic-ketamine-exposure-causes-white-matter-microstructural-abnormalities-in-adolescent-cynomolgus-monkeys
#5
Qi Li, Lin Shi, Gang Lu, Hong-Luan Yu, Fu-Ki Yeung, Nai-Kei Wong, Lin Sun, Kai Liu, David Yew, Fang Pan, De-Feng Wang, Pak C Sham
Acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. Recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. However, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter tracts that underpin the neuropathology of schizophrenia...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28556775/glutamatergic-deficit-and-schizophrenia-like-negative-symptoms-new-evidence-from-ketamine-induced-mismatch-negativity-alterations-in-healthy-male-humans
#6
Stephanie Thiebes, Gregor Leicht, Stjepan Curic, Saskia Steinmann, Nenad Polomac, Christina Andreou, Iris Eichler, Lars Eichler, Christian Zöllner, Jürgen Gallinat, Ileana Hanganu-Opatz, Christoph Mulert
BACKGROUND: Targeting the N-methyl-D-aspartate receptor (NMDAR) is a major translational approach for treating negative symptoms of schizophrenia. Ketamine comprehensively produces schizophrenia-like symptoms, such as positive, cognitive and negative symptoms in healthy volunteers. The amplitude of the mismatch negativity (MMN) is known to be significantly reduced not only in patients with schizophrenia, but also in healthy controls receiving ketamine. Accordingly, it was the aim of the present study to investigate whether changes of MMN amplitudes during ketamine administration are associated with the emergence of schizophrenia-like negative symptoms in healthy volunteers...
May 30, 2017: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/28554133/melatonin-attenuates-behavioural-deficits-and-reduces-brain-oxidative-stress-in-a-rodent-model-of-schizophrenia
#7
Adejoke Y Onaolapo, Olufemi A Aina, Olakunle James Onaolapo
Melatonin is a neurohormone that is linked to the aetiopathogenesis of schizophrenia. The aim of this study was to assess the potentials of oral melatonin supplement in the management of induced schizophrenia-like behavioural and brain oxidative status changes, using an animal model. The relative degrees of modulation of ketamine-induced behaviours by haloperidol, olanzapine or melatonin were assessed in the open-field, Y-maze, elevated plus maze and the social interaction tests. 12-week old, male mice were assigned to six groups of ten each (n=10)...
May 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28513779/the-preventive-effects-of-ascorbic-acid-supplementation-on-locomotor-and-acetylcholinesterase-activity-in-an-animal-model-of-schizophrenia-induced-by-ketamine
#8
Louyse S Damazio, Flávia R Silveira, Lara Canever, Adalberto A DE Castro, Jadne M Estrela, Josiane Budni, Alexandra I Zugno
Studies have shown that schizophrenic patients seem to have nutritional deficiencies. Ascorbic acid (AA) has an important antioxidant effect and neuromodulatory properties. The aim of this study was to evaluate the effects of AA on locomotor activity and the acetylcholinesterase activity (AChE) in an animal model of schizophrenia (SZ). Rats were supplemented with AA (0.1, 1, or 10 mg/kg), or water for 14 days (gavage). Between the 9th and 15th days, the animals received Ketamine (Ket) (25 mg/kg) or saline (i...
May 15, 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/28472198/clozapine-counteracts-a-ketamine-induced-depression-of-hippocampal-prefrontal-neuroplasticity-and-alters-signaling-pathway-phosphorylation
#9
Marion Rame, Dorian Caudal, Esther Schenker, Per Svenningsson, Michael Spedding, Thérèse M Jay, Bill P Godsil
Single sub-anesthetic doses of ketamine can exacerbate the symptoms of patients diagnosed with schizophrenia, yet similar ketamine treatments rapidly reduce depressive symptoms in major depression. Acute doses of the atypical antipsychotic drug clozapine have also been shown to counteract ketamine-induced psychotic effects. In the interest of understanding whether these drug effects could be modeled with alterations in neuroplasticity, we examined the impact of acutely-administered ketamine and clozapine on in vivo long-term potentiation (LTP) in the rat's hippocampus-to-prefrontal cortex (H-PFC) pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28468999/ketamine-induced-converged-synchronous-gamma-oscillations-in-the-cortico-basal-ganglia-network-of-non-human-primates
#10
Maya Slovik, Boris Rosin, Shay Moshel, Rea Mitelman, Eitan Schechtman, Renana Eitan, Aeyal Raz, Hagai Bergman
NMDA (N-methyl-D-aspartate) antagonists are widely used in anesthesia, pain management, schizophrenia animal model studies and recently as potential antidepressants. However the mechanisms underlying their anesthetic, psychotic, cognitive and emotional effects are still elusive. The basal-ganglia (BG) integrate input from different cortical domains through its dopamine modulated connections, to achieve optimal behavior control. NMDA antagonists have been shown to induce gamma oscillations in human EEG recordings and in rodents cortical and BG networks...
May 3, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28438555/amygdala-activity-associated-with-social-choice-in-mice
#11
Takuma Mihara, Kobina Mensah-Brown, Rosanna Sobota, Robert Lin, Robert Featherstone, Steven J Siegel
Studies suggest that the amygdala is a key region for regulation of anxiety, fear and social function. Therefore, dysfunction of the amygdala has been proposed as a potential mechanism for negative symptoms in schizophrenia. This may be due to NMDA receptor-mediated hypofunction, which is thought to be related to the pathogenesis of schizophrenia. In this study, electroencephalographic amygdala activity was assessed in mice during the three-chamber social test. This activity was also evaluated following exposure to the NMDA receptor antagonist ketamine...
April 21, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28438466/the-effect-of-n-acetylcysteine-nac-on-human-cognition-a-systematic-review
#12
REVIEW
David R Skvarc, Olivia M Dean, Linda K Byrne, Laura Gray, Stephen Lane, Matthew Lewis, Brisa S Fernandes, Michael Berk, Andrew Marriott
Oxidative stress, neuroinflammation and neurogenesis are commonly implicated as cognitive modulators across a range of disorders. N-acetylcysteine (NAC) is a glutathione precursor with potent antioxidant, pro-neurogenesis and anti-inflammatory properties and a favourable safety profile. A systematic review of the literature specifically examining the effect of NAC administration on human cognition revealed twelve suitable articles for inclusion: four examining Alzheimer's disease; three examining healthy participants; two examining physical trauma; one examining bipolar disorder, one examining schizophrenia, and one examining ketamine-induced psychosis...
April 21, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28433652/ketamine-potentiates-oxidative-stress-and-influences-behavior-and-inflammation-in-response-to-lipolysaccharide-lps-exposure-in-early-life
#13
Gislaine Z Réus, Lutiana R Simões, Gabriela D Colpo, Giselli Scaini, Jean P Oses, Jaqueline S Generoso, Alan R Prossin, Rima Kaddurah-Daouk, João Quevedo, Tatiana Barichello
Immune activation (IA) during the early neonatal period is a risk factor for the development of schizophrenia. Lipopolysaccharide (LPS) injected in neonates lead to behavioral and brain changes that persist to adult life. We investigated oxidative stress, levels of cytokines, and the locomotor activity of IA in a schizophrenia animal model in which neonatal male Wistar rats were administered with an injection of LPS (50μg/kg) on postnatal day 3 and different doses of ketamine (5, 15 and 25mg/kg) for 7days during adulthood...
April 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/28433499/changes-in-the-expression-of-metabotropic-glutamate-receptor-5-mglur5-in-a-ketamine-based-animal-model-of-schizophrenia
#14
Dariusz Zurawek, Anna Salerno-Kochan, Marta Dziedzicka-Wasylewska, Agnieszka Nikiforuk, Tomasz Kos, Piotr Popik
It has been shown that the metabotropic glutamate receptor subtype 5 (mGluR5) is functionally associated with the NMDA subtype of the glutamate receptor family (NMDA receptors). These two receptors colocalize in brain regions associated with schizophrenia. Although the role of the NMDA receptor in cognitive and negative symptoms of schizophrenia is well studied, information about the role of mGluR5 receptors in schizophrenia is sparse. In our work, we show that subchronic administration of ketamine, a well-studied, non-competitive antagonist of NMDA receptors, caused cognitive deficits in rats as shown by testing novel object recognition (NOR)...
April 19, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28421529/suppression-of-methamphetamine-self-administration-by-ketamine-pre-treatment-is-absent-in-the-methylazoxymethanol-mam-rat-model-of-schizophrenia
#15
Jana Ruda-Kucerova, Zuzana Babinska, Tibor Stark, Vincenzo Micale
Ketamine may prove to be a potential candidate in treating the widespread drug addiction/substance abuse epidemic among patients with schizophrenia. Clinical studies have shown ketamine to reduce cocaine and heroin cravings. However, the use of ketamine remains controversial as it may exacerbate the symptoms of schizophrenia. Therefore, the aim of this study is to characterize the effects of ketamine on drug addiction in schizophrenia using the methylazoxymethanol (MAM) acetate rat model on operant IV methamphetamine (METH) self-administration...
April 18, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28418641/classics-in-chemical-neuroscience-ketamine
#16
Marshall W Tyler, Harmony B Yourish, Dawn F Ionescu, Stephen J Haggarty
Ketamine, a molecule of many faces, has contributed immeasurably to numerous realms of clinical practice and scientific inquiry. From anesthesia and analgesia to depression and schizophrenia, it continues to shed light on the molecular underpinnings of pain, consciousness, and the pathophysiology of neuropsychiatric disorders. In particular, research on ketamine's mechanism of action is providing new hope in the search for therapies for treatment-resistant depression and affords insights into disorders of glutamatergic dysfunction...
June 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28408985/new-drugs-in-psychiatry-focus-on-new-pharmacological-targets
#17
REVIEW
Filippo Caraci, Gian Marco Leggio, Salvatore Salomone, Filippo Drago
The approval of psychotropic drugs with novel mechanisms of action has been rare in recent years. To address this issue, further analysis of the pathophysiology of neuropsychiatric disorders is essential for identifying new pharmacological targets for psychotropic medications. In this report, we detail drug candidates being examined as treatments for psychiatric disorders. Particular emphasis is placed on agents with novel mechanisms of action that are being tested as therapies for depression, schizophrenia, or Alzheimer's disease...
2017: F1000Research
https://www.readbyqxmd.com/read/28405711/effect-of-clozapine-on-ketamine-induced-deficits-in-attentional-set-shift-task-in-mice
#18
M Szlachta, P Pabian, M Kuśmider, J Solich, M Kolasa, D Żurawek, M Dziedzicka-Wasylewska, A Faron-Górecka
RATIONALE: Clozapine (CLZ) is an effective treatment for schizophrenia, producing improvements in both negative symptoms and cognitive impairments. Cognitive impairments can be modelled in animals by ketamine (KET) and assessed using the attentional set-shift task (ASST). OBJECTIVE: Our first aim was to determine whether CLZ improves cognitive function and reverses KET-induced cognitive impairments using the ASST. Our second aim was to assess dose dependency of these effects...
April 12, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28384469/altered-cortical-ensembles-in-mouse-models-of-schizophrenia
#19
Jordan P Hamm, Darcy S Peterka, Joseph A Gogos, Rafael Yuste
In schizophrenia, brain-wide alterations have been identified at the molecular and cellular levels, yet how these phenomena affect cortical circuit activity remains unclear. We studied two mouse models of schizophrenia-relevant disease processes: chronic ketamine (KET) administration and Df(16)A(+/-), modeling 22q11.2 microdeletions, a genetic variant highly penetrant for schizophrenia. Local field potential recordings in visual cortex confirmed gamma-band abnormalities similar to patient studies. Two-photon calcium imaging of local cortical populations revealed in both models a deficit in the reliability of neuronal coactivity patterns (ensembles), which was not a simple consequence of altered single-neuron activity...
April 5, 2017: Neuron
https://www.readbyqxmd.com/read/28350371/a-neurophysiological-perspective-on-a-preventive-treatment-against-schizophrenia-using-transcranial-electric-stimulation-of-the-corticothalamic-pathway
#20
REVIEW
Didier Pinault
Schizophrenia patients are waiting for a treatment free of detrimental effects. Psychotic disorders are devastating mental illnesses associated with dysfunctional brain networks. Ongoing brain network gamma frequency (30-80 Hz) oscillations, naturally implicated in integrative function, are excessively amplified during hallucinations, in at-risk mental states for psychosis and first-episode psychosis. So, gamma oscillations represent a bioelectrical marker for cerebral network disorders with prognostic and therapeutic potential...
March 28, 2017: Brain Sciences
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