Ketamine

Unlike traditional monoamine-based antidepressants that require weeks to exert effects, ketamine alleviates depression within hours, though its clinical use is limited by side effects. While ketamine was initially thought to work primarily through NMDA receptor (NMDAR) inhibition, our research reveals a more complex mechanism. We demonstrate that NMDAR inhibition alone cannot explain ketamine's sustained antidepressant effects, as other NMDAR antagonists like MK-801 lack similar efficacy. Instead, the (2R,6R)-hydroxynorketamine (HNK) metabolite appears critical, exhibiting antidepressant effec

Psychedelics like psilocybin and ketamine have shown great potential in treating psychiatric disorders, often producing long-lasting effects after a single dose, yet their underlying neural mechanisms remain poorly understood. Since one of the most consistent features of the psychedelic experience is the alteration in perception, this study aimed to investigate how acute doses of psychedelics influence perceptual integration. We used a free-response perceptual integration task in mice, alongside brain-wide mapping of drug-responsive populations using activity-dependent gene expression and calc

…Psilocybin and ketamine induce antidepressant effects which last for days or weeks after a single dose, yet their pharmacology is distinct. Psilocybin is a classical psychedelic which acts via 5-HT2A receptor agonism, and ketamine is a NMDA receptor antagonist with dissociative hallucinatory properties. Our goal was to increase our understanding of acute drug effects in mice. We treated wildtype mice with psilocybin (1 mg/kg, i.p.) or ketamine (30 mg/kg, i.p.) and analyzed their behavior in

Ketamine has gained significant attention as a treatment for depression. However, it is also associated with undesirable side effects. In our preclinical study, we explored the behavioral effects of ketamine enantiomers, hypothesizing that R-ketamine will have fewer behavioral effects than S-ketamine. During repeated intermittent treatment with doses relevant to antidepressant therapy, we examined behaviors that are regarded as behavioral markers of unwanted effects: locomotor stimulation and sensitization, ataxia, and disruption of natural behaviors (grooming and rearing). Male Wistar rats we

Ketamine, a rapid acting antidepressant ( Zarate et al. 2006), induces acute hippocampal volumetric changes ( Höflich et al. 2021). Considering the observed link between major depressive disorder (MDD) and a lower hippocampal volume (MacQueen et al. 2011), investigating ketamine-induced neuroplastic changes in this region may contribute to understand treatment effects.In a placebo-controlled, single-blind, crossover study 36 healthy subjects (17males, 23.8±3.75 years) received either 0.5mg/kg racemic ketamine or placebo 4 hours before MRI scans. FreeSurfer7.1 was used for the hippocampal subfi

I show new idea how mu-opioids and high prenatal nicotine cause respiratory slowdown linked toslow wave sleep. A high dose of mu-opioids overstimulates the medial habenula whichactivates the interpeduncular nucleus. The IPN causes respiratory depression via its output toPAG, DRN, MRN, or LPO-RMTg.SWS is linked to a natural slowdown of respiration and heart rate. The MHb and rostromedial tegmental nucleus are known for high amount of mu-opioid receptors. Both MHb and RMTg were proposed to be activated in the neural circuit that promotes SWS, rest, immune defense and recovery (Vadovičová, 2015).

…NMDA/glutamate receptor antagonist ketamine, can induce psychotic symptoms in healthy subjects and exacerbate them in schizophrenia patients. Taking

Parkinson’s disease (PD) is usually thought of as a motor disorder, although non-motor symptoms may precede the motor manifestations and are a key component of the PD. Among these, depression and anxiety are most prevalent symptoms and caused a greater symptomatic burden in women than in men. A dysfunctional serotonin (5-HT) system is generally considered a risk factor for depression. We propose the ventromedial prefrontal cortex (vmPFC)-dorsal raphe nucleus (DR) circuit as the key player underlying depressive/anxious disorders in PD, by virtue of its reciprocal connectivity. Female mice overe

…antidepressants, exemplified by ketamine, has garnered attention, yet the intricate underlying processes remain incompletely understood.This study systematically evaluated the acute effects of ketamine (10 mg/kg, i.p.) and fluoxetine (3 x 10 mg/kg, i.p.) on depression-like behavior in animal models subjected to chronic restraint stress (CRS, 6 weeks) and chr

N-methyl-D-aspartate (NMDA) receptors are critical for cortical function and their dysfunctions are implicated in psychiatric disorders. Previous modeling studies focused on their role in generating long-timescale neuronal dynamics for working memory or evidence accumulation. Less is known about how NMDA-mediated synapses shape oscillatory dynamics in local field potentials (LFPs) or non-invasive E/MEG recordings, and how changes in NMDA transmission can be inferred from such measures of mass activity. To address these issues, we developed a recurrent network model of excitatory (E) and inhibi

…(Carhart-Harris et al., 2017) Ketamine exhibits robust and enduring antidepressant properties both in patients and preclinical models. (Krystal et al., 2013). Sleep patterns are often affected by depressive disorders, making wireless EEG a valuable too

…(Carhart-Harris et al., 2017) Ketamine exhibits robust and enduring antidepressant properties both in patients and preclinical models. (Krystal et al., 2013). Sleep patterns are often affected by depressive disorders, making wireless EEG a valuable

…Subanesthetic ketamine is a promising rapid-acting TRD pharmacotherapy, but optimal treatment frequency remains unclear. The present study aims to better understand the effects of an acute (single dose) and chronic (one week daily) 10mg/kg ketamine treatment on hippocampal plasticity, a key mechanism impaired in depression, in a putative TRD model: the Wistar-Kyoto (WKY) rat exposed to chronic mild stress (CMS). Rats were e

…Ketamine (KET) is a fast-acting antidepressant that transiently inhibits N-methyl-d-aspartate receptors (NMDARs) to produce its antidepressant effects. KET is rapidly metabolised to hydroxynorketamine (HNK), which reduces depressive behaviour in rodents. HNK has been shown to

Spreading Depolarizations (SDs) are electrographic events that arise post-stroke and correlate with worsening outcome. The haemodynamic response to SD is vasodilation in well perfused tissue. However, SDs induce hypoperfusion in ischemic tissue, further decreasing the viability of ‘at risk’ tissue.Traditional metal-based electrodes are limited in their ability to faithfully record DC-coupled potential shifts including SD. In contrast, Graphene micro-transistor arrays (gSGFETs) precisely record SDs without signal attenuation, distortion or voltage drift; and their transparency allows simultaneo

Ketamine is a rapid-acting antidepressant often accompanied with different cognitive side effects. Previous research has generated mixed results regarding its effects on distinct types of memory. Here, we investigated the effects of an antidepressant dose (10 mg/kg) of ketamine on encoding, retrieval, and modulation processes in an implicit and an explicit memory task in adult male Wistar rats (n = 60). Ketamine (IP) was administered 30 minutes either before the acquisition, retrieval, or extinction phase of auditory fear conditioning (implicit task). Similarly, different groups of animals rec

…We showed that repeated exposure to ketamine causes the loss of the perineuronal nets (PNN) and reestablishes juvenile-like plasticity in the adult visual cortex (V1) (Venturino et al, 2021). Microglia enable the PNN dismantling and their depletion prevented this effect. In a side investigation, we observed that under acute ketamine exposure, microglia adapt in a sex-dependent manner. Thus, is there a sex-specific effect of how microglia modulate neuronal activity? Here, we show a sex-specific adaptation of the neu

Ketamine is a non-competitive NMDA antagonist with hallucinogenic, analgesic and anesthetic properties. It has been repurposed for the treatment of depression, but its narcotic properties have made it attractive for recreational abuse. Consistent with the findings that non-competitive NMDA antagonists disrupt memory, studies in humans and monkeys have demonstrated impartment in cognitive functions, including memory, even with low doses of ketamine. Previously, our laboratory has shown, in macaques, that transient inactivation of the hippocampus by intracerebral infusion of the GABAA agonist mu

Mood disorders such as depression or anxiety disorders are the most prevalent psychiatric diseases and represent the highest level of avoidable health-care cost in first world countries. Nonetheless, the biological foundation of these diseases is only poorly understood despite decades of research. Most clinically used antidepressants target the monoamine system and aim at either raising the levels of monoamines (serotonin, norepinephrine, dopamine) in the synaptic cleft through inhibition of reuptake or act on monoaminergic receptors. However, it takes several weeks until an antidepressant eff

The discovery of LSD launched a new era of psychedelic research. The number of clinical trials is consistently increasing since psychedelics' sustained therapeutic effects seem to be promising in the reduction of symptoms of various neuropsychiatric disorders. In humans, the acute neuronal effect of psychedelics is often measured by fMRI and EEG signals and their behaviour through subjective questionnaires. In rodents, behavioural testing is much more precise. However, fMRI is only possible in anaesthetized animals which poses its own limitations. Researchers have circumvented this challenge

The use of molecular imaging, particularly PET and SPECT, has significantly transformed the treatment of schizophrenia with antipsychotic drugs since the late 1980s. It has offered insights into the links between drug target engagement, clinical effects, and side effects. A therapeutic window for receptor occupancy is established for antipsychotics, yet there is a divergence of opinions regarding the importance of blood levels, with many downplaying their significance. As a result, the role of therapeutic drug monitoring (TDM) as a personalized therapy tool is often underrated. Since molecular

…mobility leads to depression; how ketamine tames depression by blocking burst firing in the brain’s antireward center; and, how glia-neuron interaction plays a surprising role in this process. I will also present our recent work on the mecha

…mobility leads to depression; how ketamine tames depression by blocking burst firing in the brain’s antireward center; and, how glia-neuron interaction plays a surprising role in this process. I will also present our recent work on the mecha

…tricyclic as well as fast-acting ketamine, directly bind to TRKB, thereby promoting TRKB translocation to synapt