Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology

Stone, James; Dietrich, Craige; Edden, Richard A.E.; Mehta, Mitul A.; Simoni, Sara De; Reed, Laurence; Krystal, John H.; Nutt, David; Barker, Gareth J.

doi:10.1038/mp.2011.171

Cited by 258 publications

(227 citation statements)

References 10 publications

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“…Both mechanisms lead to dendritic spine growth, followed by enhanced synaptic plasticity, neurotransmission and functional connectivity [56] . This speculation that YY-23 may enhance synaptic neurotransmission was not only supported by numerous observations related to the effects of other NMDA receptor antagonists [58][59][60] but was also confirmed by our previous work, which showed the significant ability of YY-23 to reverse the decreased burst firing induced by CMS [24] . Regarding the downstream mechanism, we have noted interesting changes in some of the signaling pathways downstream of the glutamate receptors after treatment with YY-23, but additional work is needed to draw definitive conclusions regarding these changes.…”

Section: Discussionsupporting

confidence: 63%

Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice

Zhang

Guo

et al. 2015

Acta Pharmacol Sin

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Aim: N-methyl-D-aspartic acid (NMDA) receptor modulators have shown promising results as potential antidepressant agents, whereas timosaponins extracted from the Chinese herb Rhizoma Anemarrhenae exhibit antidepressant activities. In the present study we examined whether YY-23, a modified metabolite of timosaponin B-III, could affect NMDA receptors in rat hippocampal neurons in vitro, and evaluated its antidepressant-like effects in stressed mice. Methods: NMDA-induced currents were recorded in acutely dissociated rat hippocampal CA1 neurons using a whole-cell recording technique. C57BL/6 mice were exposed to a 6-week chronic mild stress (CMS) or a 10-d chronic social defeat stress (CSDS). The stressed mice were treated with YY-23 (20 mg·kg -1 ·d -1 ) or a positive-control drug, fluoxetine (10 mg·kg -1 ·d -1 ) for 3 weeks. Behavioral assessments were carried out every week. Results: In acutely dissociated rat hippocampal CA1 neurons, YY-23 selectively and reversibly inhibited NMDA-induced currents with an EC 50 value of 2.8 μmol/L. This inhibition of NMDA-induced currents by YY-23 was non-competitive, and had no features of voltagedependency or use-dependency. Treatment of the stressed mice with YY-23 not only reversed CMS-induced deficiency of sucrose preference and immobility time, and CSDS-induced reduction of social interaction, but also had faster onset as compared to fluoxetine. Conclusion: YY-23 is a novel non-competitive antagonist of NMDA receptors with promising rapid antidepressant-like effects in mouse models of CMS and CSDS depression.

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Section: Discussionsupporting

confidence: 63%

Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice

Zhang

Guo

et al. 2015

Acta Pharmacol Sin

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“…However, following a long course of illness, chronic schizophrenia patients showed significant reduction in PFC GBCr (Anticevic et al, 2015a;Cole et al, 2011). These observations suggest the possibility of increased overall glutamate synaptic strength early in the course of the disorder, comparable to NMDA antagonists' effect-which temporally increase glutamate activities as well as GBCr in healthy volunteers (Anticevic et al, 2015a;Driesen et al, 2013a;Driesen et al, 2013b;Rowland et al, 2005;Stone et al, 2012). However, the chronic glutamate activation-owing to NMDA hypofunction and/or psychopathology-related stress-precipitates PFC synaptic dysconnectivity and GBCr reduction (Krystal and Anticevic, 2015).…”

Section: Discussionmentioning

confidence: 87%

Ketamine Treatment and Global Brain Connectivity in Major Depression

Abdallah

Averill

Collins

et al. 2016

Neuropsychopharmacol

249

216

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Capitalizing on recent advances in resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) and the distinctive paradigm of rapid mood normalization following ketamine treatment, the current study investigated intrinsic brain networks in major depressive disorder (MDD) during a depressive episode and following treatment with ketamine. Medication-free patients with MDD and healthy control subjects (HC) completed baseline rs-fcMRI. MDD patients received a single infusion of ketamine and underwent repeated rs-fcMRI at 24 h posttreatment. Global brain connectivity with global signal regression (GBCr) values were computed as the average of correlations of each voxel with all other gray matter voxels in the brain. MDD group showed reduced GBCr in the prefrontal cortex (PFC) but increased GBCr in the posterior cingulate, precuneus, lingual gyrus, and cerebellum. Ketamine significantly increased GBCr in the PFC and reduced GBCr in the cerebellum. At baseline, 2174 voxels of altered GBCr were identified, but only 310 voxels significantly differed relative to controls following treatment (corrected αo0.05). Responders to ketamine showed increased GBCr in the lateral PFC, caudate, and insula. Follow-up seed-based analyses illustrated a pattern of dysconnectivity between the PFC/subcortex and the rest of the brain in MDD, which appeared to normalize postketamine. The extent of the functional dysconnectivity identified in MDD and the swift and robust normalization following treatment suggest that GBCr may serve as a treatment response biomarker for the development of rapid acting antidepressants. The data also identified unique prefrontal and striatal circuitry as a putative marker of successful treatment and a target for antidepressants' development.

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“…In studi su animali, basse dosi di ketamina sono state associate con un rapido incremento della concentrazione extracellulare di glutammato e dopamina nella corteccia prefrontale (Moghaddam 1997) e nella corteccia cingolata anteriore (Stone 2012), con conseguente attivazione di una neurotrasmissione eccitatoria. Altri meccanismi di azione includono l'attivazione dell'acido amminometil-isoxazolone-proprionato (AMPA) e di potenziali motori evocati (Di Lazzaro 2003).…”

Section: La Ketamina Come Nuovo Antidepressivo Ad Azione Rapida: Le Aunclassified

La ketamina come antidepressivo ad azione rapida: controversia e implicazioni [translation of “Ketamine as a rapid antidepressant: the debate and implications” by Dr. Giacomo Galli and Dr. Serena Saraceni]

Ho¹,

Zhang²

2016

BJPsych advances

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Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology

Cited by 258 publications

References 10 publications

Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice

Timosaponin derivative YY-23 acts as a non-competitive NMDA receptor antagonist and exerts a rapid antidepressant-like effect in mice

Ketamine Treatment and Global Brain Connectivity in Major Depression

La ketamina come antidepressivo ad azione rapida: controversia e implicazioni [translation of “Ketamine as a rapid antidepressant: the debate and implications” by Dr. Giacomo Galli and Dr. Serena Saraceni]

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