Excitatory-inhibitory imbalance has been identified within specific brain microcircuits in models of Rett syndrome (RTT) and other autism spectrum disorders (ASDs). However, macrocircuit dysfunction across the RTT brain as a whole has not been defined. To approach this issue, we mapped expression of the activity-dependent, immediate-early gene product Fos in the brains of wild-type (Wt) and...
The recreational use of ketamine is increasing in popularity due to its dissociative and paralytic effects, ease of availability and low cost. However, serious and frequently irreversible damage to the urinary tract is a recently recognised side effect of recreational ketamine use. The authors present a case of a young male patient with a 2-year history of troublesome lower urinary tract...
Increasing preclinical and clinical evidence underscores the strong and rapid antidepressant properties of the glutamate-modulating NMDA receptor antagonist ketamine. Targeting the glutamatergic system might thus provide a novel molecular strategy for antidepressant treatment. Since glutamate is the most abundant and major excitatory neurotransmitter in the brain, pathophysiological changes in...
Objective To study the role of L-arginine/nitric oxide (NO) pathway in the antidepressant effects of ketamine. Methods Forty two male Wistar rats (200-250 g) were equally randomized into 7 groups (n=6): control group (C group), L-Arginine (a precursor of NO) group (LA group), L-NAME(an non-selectivity inhibitor of NO synthase) group (LN group), ketamine 3 mg/kg group (K3 group), ketamine 10...
Luckenbaugh DA, Ibrahim L, Brutsche N, Franco‐Chaves J, Mathews D, Marquardt CA, Cassarly C, Zarate CA Jr. Family history of alcohol dependence and antidepressant response to an N ‐methyl‐ d ‐aspartate antagonist in bipolar depression. Bipolar Disord 2012: 14: 880–887. Published 2012. This article is a U.S. Government work and is in the public domain in the USA. Objectives: Both ketamine and...
Background The influence of psychoactive drugs on the central nervous system has been investigated with positron emission tomography and task-related functional magnetic resonance imaging. However, it is not known how these drugs affect the intrinsic large-scale interactions of the brain (resting-state functional magnetic resonance imaging connectivity). In this study, the effect of low-dose...
This paper presents a model-based investigation of mechanisms underlying the reduction of mismatch negativity (MMN) amplitudes under the NMDA-receptor antagonist ketamine. We applied dynamic causal modeling and Bayesian model selection to data from a recent ketamine study of the roving MMN paradigm, using a cross-over, double-blind, placebo-controlled design. Our modeling was guided by a...
RationaleBoth glutamate and serotonin (5-HT) play a key role in the pathophysiology of emotional biases. Recent studies indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine and the 5-HT receptor agonist psilocybin are implicated in emotion processing. However, as yet, no study has systematically compared their contribution to emotional biases.ObjectivesThis study...
Methoxetamine, the N-ethyl derivative of ketamine, is a novel recreational drug that is not at present subject to restrictive regulations in most countries. To our knowledge, no case of methoxetamine abuse has been published to date in the scientific literature, and the only sources of information are illegal drug users' Web discussion forums. We report the first case of analytically confirmed...
The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD). In rats, ketamine selectively increased electroencephalogram (EEG) slow wave activity (SWA) during non-rapid eye movement (REM) sleep and altered central brain-derived neurotrophic factor (BDNF) expression. Taken together, these findings suggest...
Ketamine is a N-methyl-D-aspartic acid (NMDA) antagonist that has been associated with temporary clinical improvement in patients with depression. Studies using magnetic resonance spectroscopy (MRS) have shown that major depression is associated with decreased levels of glutamate and glutamine (Glx) in the anterior cingulate cortex, which normalize with clinical recovery. The present study...
Long-term regular use of ketamine has been reported to be associated with severe symptomatic urinary tract problems. Methoxetamine, an arylcyclohexylamine derivative of ketamine, is marketed as a "bladder safe" derivative of ketamine, and no cases of acute toxicity following analytically confirmed methoxetamine use have been reported to date. We report here a case series of three individuals...
Ketamine is an NMDA antagonist and dissociative anesthetic that has been shown to display rapid acting and prolonged antidepressant activity in small-scale human clinical trials. Ketamine also binds to σ receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine the involvement of σ receptors in the...
The FASEB JournalApril 1, 2012Luli R Akinfiresoye, D. M. Lovinger, Y. Tizabi
Studies have shown that therapeutics that act on the glutamatergic system could provide a novel mechanistic approach for the treatment of depression. We previously reported that ketamine, an NMDA antagonist, has a rapid and lasting antidepressant effect both acutely and chronically on depressive‐like behavior in Wistar‐Kyoto (WKY) rats ( Soc Neurosci Abst 2008) . Other studies had suggested...
To study the deleterious effects of ketamine and the potential interaction effects between ethanol and ketamine on the cerebellum, functional magnetic resonance imaging (fMRI) tests were performed on the habitual ketamine users (n = 3) when they flexed and extended their upper limbs. Another fMRI test was performed on the same participants in which they consumed alcohol (12%, 200 mL) 1 h before...
Psychotomimetics like the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine and the 5-hydroxytryptamine2A receptor (5-HT(2A)R) agonist psilocybin induce psychotic symptoms in healthy volunteers that resemble those of schizophrenia. Recent theories of psychosis posit that aberrant encoding of prediction errors (PE) may underlie the expression of psychotic symptoms. This study used a...
On the basis of the material available both in the scientific literature and on the web, this paper aims to provide a pharmacological, chemical and behavioural overview of the novel compound methoxetamine. This is a dissociative drug related to ketamine, with a much longer duration of action and intensity of effects. A critical discussion of the availability of information on the web of...
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • (R,S)‐ketamine is a phencyclidine derivative that was initially developed as an anaesthetic agent and which is currently being studied in the treatment of pain and depression. After administration, the drug is extensively N‐demethylated to (R,S)‐norketamine. The pharmacokinetics of ketamine and norketamine have been extensively studied in volunteers...
Preclinical studies suggest that ketamine-induced psychopathology is mediated, in part, by increased glutamate release, hypothesized to occur via inhibition of GABAergic interneurons. Using proton magnetic resonance spectroscopy (1H-MRS), we tested this hypothesis in healthy humans. Ketamine increased anterior cingulate cortex glutamate levels, which correlated with the degree of positive...
Out-of-body experiences present a unique paradigm to investigate cognitive and neural mechanisms of bodily-self processes and their disorders. Previous work on out-of-body experiences associated with sleep paralysis supported a model in which illusory movement experiences reflect disrupted bodily-self integration generating anomalous vestibular and motor sensations. Further disintegration and...