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d-serine ketamine

Mark J Millan, Jean-Michel Rivet, Alain Gobert
The highly-interconnected and neurochemically-rich frontal cortex plays a crucial role in the regulation of mood and cognition, domains disrupted in depression and other central nervous system disorders, and it is an important site of action for their therapeutic control. For improving our understanding of the function and dysfunction of the frontal cortex, and for identifying improved treatments, quantification of extracellular pools of neuromodulators by microdialysis in freely-moving rodents has proven indispensable...
October 17, 2016: Journal of Psychopharmacology
B Romeo, W Choucha, P Fossati, J-Y Rotge
OBJECTIVE: The aim of this review was to determine the clinical and biological predictors of the ketamine response. METHODS: A systematic research on PubMed and PsycINFO database was performed without limits on year of publication. RESULTS: The main predictive factors of ketamine response, which were found in different studies, were (i) a family history of alcohol dependence, (ii) unipolar depressive disorder, and (iii) neurocognitive impairments, especially a slower processing speed...
September 9, 2016: L'Encéphale
Nagendra S Singh, Ewelina Rutkowska, Anita Plazinska, Mohammed Khadeer, Ruin Moaddel, Krzysztof Jozwiak, Michel Bernier, Irving W Wainer
D-Serine is an endogenous NMDA receptor co-agonist that activates synaptic NMDA receptors modulating neuronal networks in the cerebral cortex and plays a key role in long-term potentiation of synaptic transmission. D-serine is associated with NMDA receptor neurotoxicity and neurodegeneration and elevated D-serine concentrations have been associated with Alzheimer's and Parkinsons' diseases and amyotrophic lateral sclerosis. Previous studies have demonstrated that the ketamine metabolites (rac)-dehydronorketamine and (2S,6S)-hydroxynorketamine decrease intracellular D-serine concentrations in a concentration dependent manner in PC-12 cells...
2016: PloS One
M R Hudson, G Rind, T J O'Brien, N C Jones
Recent heuristic models of schizophrenia propose that abnormalities in the gamma frequency cerebral oscillations may be closely tied to the pathophysiology of the disorder, with hypofunction of N-methyl-d-aspartate receptors (NMDAr) implicated as having a crucial role. Prepulse inhibition (PPI) is a behavioural measure of sensorimotor gating that is disrupted in schizophrenia. We tested the ability for antipsychotic drugs with diverse pharmacological actions to (1) ameliorate NMDAr antagonist-induced disruptions to gamma oscillations and (2) attenuate NMDAr antagonist-induced disruptions to PPI...
2016: Translational Psychiatry
Meiling Zhang, Congcong Wen, Yuan Zhang, Fa Sun, Shuanghu Wang, Jianshe Ma, Kezhi Lin, Xianqin Wang, Guanyang Lin, Lufeng Hu
This study aims to evaluate the effect of ketamine on rats by examining the differences in serum metabolites between ketamine abuse group (Ket-group) and control group (Con-group). Compared to the Con-group, the level of phosphate, propanoic acid, ribitol and d-fructose of the Ket-group increased after continuous intraperitoneal administration of ketamine for 7 days, while the level of alanine, glycine, butanoic acid, valine, l-serine, l-proline, mannonic acid, octadecanoic acid and cholesterol decreased. After 14 days' administration, the level of alanine, butanoic acid, valine, l-leucine, phosphate, l-serine, l-threonine, propanetricarboxylic acid, hexadecanoic acid and oleic acid of the ketamine group increased while the level of mannonic acid, octadecanoic acid and cholesterol decreased...
December 1, 2015: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
María Teresa Rivera-García, Carolina López-Rubalcava, Silvia L Cruz
RATIONALE: Toluene is a misused inhalant with hallucinogenic properties and complex effects. Toluene blocks N-methyl-D-aspartate (NMDA) receptors, releases dopamine (DA), and modifies several neurotransmitter levels; nonetheless, the mechanism by which it produces hallucinations is not well characterized. OBJECTIVES: This study aims (a) to study toluene's effects on the 5-HT2A-mediated head-twitch response (HTR), dopamine (DA), and serotonin (5-HT) tissue levels in discrete brain regions; (b) to compare the actions of toluene, ketamine, and 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) on HTR; and (c) to study the pharmacological blockade of toluene's and ketamine's effects by selective drugs...
October 2015: Psychopharmacology
Benoit Silvestre de Ferron, Khaled-Ezaheir Bennouar, Myriam Kervern, Stéphanie Alaux-Cantin, Alexandre Robert, Kevin Rabiant, Johann Antol, Mickaël Naassila, Olivier Pierrefiche
BACKGROUND: Binge drinking is common in adolescents, but the impact of only a few binges on learning and memory appears underestimated. Many studies have tested the effects of long and intermittent ethanol exposure on long-term synaptic potentiation, and whether long-term synaptic depression is affected remains unknown. METHODS: We studied the effects of one (3 g/kg, i.p.; blood ethanol content of 197.5±19 mg/dL) or 2 alcohol intoxications (given 9 hours apart) on adolescent rat's memory and synaptic plasticity in hippocampus slice after different delay...
January 2016: International Journal of Neuropsychopharmacology
Nagendra S Singh, Michel Bernier, Simonetta Camandola, Mohammed A Khadeer, Ruin Moaddel, Mark P Mattson, Irving W Wainer
BACKGROUND AND PURPOSE: Patients with major depressive disorder receiving racemic ketamine, (R,S)-ketamine, experience transient increases in Clinician-Administered Dissociative States Scale scores and a coincident drop in plasma d-serine levels. The results suggest that (R,S)-ketamine produces an immediate, concentration-dependent pharmacological effect on d-serine plasma concentrations. One potential source of this effect is (R,S)-ketamine-induced inhibition of the transporter ASCT2, which regulates intracellular d-serine concentrations...
July 3, 2015: British Journal of Pharmacology
Lorenz Deutschenbaur, Johannes Beck, Anna Kiyhankhadiv, Markus Mühlhauser, Stefan Borgwardt, Marc Walter, Gregor Hasler, Daniel Sollberger, Undine E Lang
Major depression is a common, recurrent mental illness that affects millions of people worldwide. Recently, a unique fast neuroprotective and antidepressant treatment effect has been observed by ketamine, which acts via the glutamatergic system. Hence, a steady accumulation of evidence supporting a role for the excitatory amino acid neurotransmitter (EAA) glutamate in the treatment of depression has been observed in the last years. Emerging evidence indicates that N-methyl-D-aspartate (NMDA), group 1 metabotropic glutamate receptor antagonists and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) agonists have antidepressant properties...
January 4, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Congcong Wen, Meiling Zhang, Jianshe Ma, Lufeng Hu, Xianqin Wang, Guanyang Lin
In this study, we developed a urine metabonomic method, based on gas chromatography-mass spectrometry (GC-MS), to evaluate the effect of ketamine on rats. Pattern recognition analysis, including both principal component analysis and partial least squares discriminate analysis revealed that ketamine (50 mg/kg) induced metabolic perturbations. Compared with the control group, at day 7, the level of alanine, butanoic acid, glutamine, butanedioic, trimethylsiloxy, L-aspartic acid, D-glucose, cholesterol, acetamide, and oleic acid of the ketamine group was increased, while the level of 2,3,4-trihydroxybutyric acid, benzeneacetic acid, threitol, ribitol, xylitol, and glycine decreased...
2015: Drug Design, Development and Therapy
Mauricio P Cunha, Francis L Pazini, Fabiana K Ludka, Julia M Rosa, Ágatha Oliveira, Josiane Budni, Ana B Ramos-Hryb, Vicente Lieberknecht, Luis E B Bettio, Maria D Martín-de-Saavedra, Manuela G López, Carla I Tasca, Ana Lúcia S Rodrigues
The modulation of N-methyl-D-aspartate receptor (NMDAR) and L-arginine/nitric oxide (NO) pathway is a therapeutic strategy for treating depression and neurologic disorders that involves excitotoxicity. Literature data have reported that creatine exhibits antidepressant and neuroprotective effects, but the implication of NMDAR and L-arginine/nitric oxide (NO) pathway in these effects is not established. This study evaluated the influence of pharmacological agents that modulate NMDAR/L-arginine-NO pathway in the anti-immobility effect of creatine in the tail suspension test (TST) in mice...
April 2015: Amino Acids
Ruin Moaddel, David A Luckenbaugh, Ying Xie, Alma Villaseñor, Nancy E Brutsche, Rodrigo Machado-Vieira, Anuradha Ramamoorthy, Maria Paz Lorenzo, Antonia Garcia, Michel Bernier, Marc C Torjman, Coral Barbas, Carlos A Zarate, Irving W Wainer
RATIONALE: (R,S)-ketamine is a rapid and effective antidepressant drug that produces a response in two thirds of patients with treatment-resistant depression (TRD). The underlying biochemical differences between a (R,S)-ketamine responder (KET-R) and non-responder (KET-NR) have not been definitively identified but may involve serine metabolism. OBJECTIVES: The aim of the study was to examine the relationship between baseline plasma concentrations of D-serine and its precursor L-serine and antidepressant response to (R,S)-ketamine in TRD patients...
January 2015: Psychopharmacology
Débora K Rieger, Ana Paula Costa, Josiane Budni, Morgana Moretti, Sabrina Giovana Rocha Barbosa, Kyria S Nascimento, Edson H Teixeira, Benildo S Cavada, Ana Lúcia S Rodrigues, Rodrigo B Leal
Lectins recognize and reversibly bind to carbohydrates attached to proteins and lipids modulating a variety of signaling pathways. We previously showed that ConBr, a lectin from Canavalia brasiliensis seeds, produced an antidepressant-like effect in mice by modulating the monoaminergic neurotransmitter systems. Moreover, ConBr blocked hippocampal neurotoxicity induced by quinolinic acid in vivo and by glutamate in vitro, suggesting a neuroprotective activity of ConBr via glutamatergic system modulation. Therefore, the present study was undertaken to investigate the involvement of the N-methyl-D-aspartate (NMDA) receptor and the L-arginine-nitric oxide (NO) pathway in the antidepressant-like action displayed by ConBr in the forced swimming test (FST)...
July 2014: Pharmacology, Biochemistry, and Behavior
Helena M Abelaira, Gislaine Z Réus, Morgana V Neotti, João Quevedo
The aim of this study was to characterize the mTOR signaling cascade in depression and the actions that antidepressant drugs have on this pathway. Herein, a literature review was performed by verification and comparison of textbooks and journal articles that describe the characterization of the mTOR signaling cascade and its relationship to depression and antidepressant drugs, especially ketamine. Postmortem studies have shown robust deficits in the mammalian target of rapamycin (mTOR) signaling in the prefrontal cortex of subjects diagnosed with major depressive disorder...
April 17, 2014: Life Sciences
Im-Joon Shin, Sung Un Son, Hyunwoo Park, Yoorim Kim, Sung Hyun Park, Kelley Swanberg, Joo-Yeon Shin, Sang-Kyu Ha, Yoonju Cho, Soo-Yong Bang, Jae-Hwan Lew, Seung-Hun Cho, Sungho Maeng
Radix Polygalae (the root of Polygala tenuifolia) is a herb widely used in traditional Asian medicine that is thought to exert a variety of neuropsychiatric effects. Radix Polygalae extract can protect against N-methyl D-aspartate (NMDA) neurotoxicity and induce brain-derived neurotrophic factor (BDNF) expression, suggesting modulatory roles at glutamatergic synapses and possible antidepressant action. In accordance with this hypothesis, Radix Polygalae extract demonstrated antidepressant-like effects in 8-week-old male C57Bl/6 mice by decreasing behavioral despair in the forced swim and tail suspension tasks and increasing hedonic-like behavior in the female urine sniffing test 30 minutes after a single oral administration of 0...
2014: PloS One
Mark J Niciu, Ioline D Henter, David A Luckenbaugh, Carlos A Zarate, Dennis S Charney
The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression. These effects are in direct contrast to the more modest effects seen after weeks of treatment with classic monoaminergic antidepressants. Numerous open-label and case studies similarly validate ketamine's antidepressant properties. These clinical findings have been reverse-translated into preclinical models in an effort to elucidate ketamine's antidepressant mechanism of action, and three important targets have been identified: mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (eEF2), and glycogen synthase kinase-3 (GSK-3)...
2014: Annual Review of Pharmacology and Toxicology
Marie Naughton, Gerard Clarke, Olivia F O'Leary, John F Cryan, Timothy G Dinan
INTRODUCTION: Recent research has seen low-dose ketamine emerge as a novel, rapid-acting antidepressant. Ketamine, an N-methy-d-aspartate (NMDA) receptor antagonist, leads to effects on the glutamatergic system and abnormalities in this neurotransmittor system are present in depression. This article aims to (1) review the clinical literature on low-dose ketamine as a rapid-acting antidepressant in affective disorders, (2) provide a critical overview of the limitations of ketamine and research attempts to overcome these (3) discuss the proposed mechanisms of action of ketamine and (4) point towards future research directions...
March 2014: Journal of Affective Disorders
Y Xie, G M Alexander, R J Schwartzman, N Singh, M C Torjman, M E Goldberg, I W Wainer, R Moaddel
A validated LC-MS/MS method was developed for the determination of d -Serine in human plasma. The method was fully validated for use with human plasma samples and was linear from 0.19 nmol/ml to 25 nmol/ml. The coefficient of variation was ≤5% for the high QC standards and ≤8% for the low QC standards in plasma. d -Serine and l -serine were resolved by pre-column derivatization using (R)-1-Boc-2-piperidine carbonyl chloride as the derivatizating agent. The method was used to determine the concentration of d-serine in plasma samples obtained in patients receiving a continuous 5-day intravenous infusion of (R,S)-ketamine...
February 2014: Journal of Pharmaceutical and Biomedical Analysis
P A Zunszain, M A Horowitz, A Cattaneo, M M Lupi, C M Pariante
Major depressive disorder is an extremely debilitating condition affecting millions of people worldwide. Nevertheless, currently available antidepressant medications still have important limitations, such as a low response rate and a time lag for treatment response that represent a significant problem when dealing with individuals who are vulnerable and prone to self-harm. Recent clinical trials have shown that the N-methyl-D-aspartate receptor antagonist, ketamine, can induce an antidepressant response within hours, which lasts up to 2 weeks, and is effective even in treatment-resistant patients...
December 2013: Molecular Psychiatry
Ashley N Hanks, Keith Dlugolenski, Zoë A Hughes, Patricia A Seymour, Mark J Majchrzak
Social withdrawal is one of several negative symptoms of schizophrenia, all of which are poorly treated by current therapies. One challenge in developing agents with efficacy against negative symptoms is the lack of suitable preclinical models. The social approach test was used as the basis for developing an assay to test emerging therapies for negative symptoms. NMDA antagonists and dopamine agonists have been used extensively to produce or disrupt behaviors thought to be rodent correlates of positive and cognitive symptoms of schizophrenia...
September 1, 2013: Behavioural Brain Research
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