scholarly journals Ketamine effects on anxiety and fear-related behaviors: current literature evidence and new findings

2019 ◽  
Author(s):  
Gabriela P. Silote ◽  
Sabrina F.S. de Oliveira ◽  
Deidiane E. Ribeiro ◽  
Mayara S. Machado ◽  
Roberto Andreatini ◽  
...  
Keyword(s):  
Nmda Antagonist ◽  
Inhibitory Avoidance ◽  
Nmda Receptor Antagonist ◽  
Mixed Effects ◽  
Antidepressant Effect ◽  
List Type ◽  
Mk 801 ◽  
New Findings ◽  
Male Wistar Rats ◽  
Animal Tests

AbstractKetamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, presents rapid and sustained antidepressant effect in clinical and preclinical studies. Regarding ketamine effects on anxiety, there is a widespread discordance among pre-clinical studies. To address this issue, the present study reviewed the literature (electronic database MEDLINE) to summarize the profile of ketamine effects in animal tests of anxiety/fear. We found that ketamine anxiety/fear-related effects may depend on the anxiety paradigm, schedule of ketamine administration and tested species. Moreover, there was no report of ketamine effects in animal tests of fear related to panic disorder (PD). Based on that finding, we evaluated if treatment with ketamine and another NMDA antagonist, MK-801, would induce acute and sustained (24 hours later) anxiolytic and/or panicolytic-like effects in animals exposed to the elevated T-maze (ETM). The ETM evaluates, in the same animal, conflict-evoked and fear behaviors, which are related, respectively, to generalized anxiety disorder and PD. Male Wistar rats were systemically treated with racemic ketamine (10, 30 and 80 mg/kg) or MK-801 (0.05 and 0.1 mg/kg) and tested in the ETM in the same day or 24 hours after their administration. Ketamine did not affect the behavioral tasks performed in the ETM acutely or 24 h later. MK-801 impaired inhibitory avoidance in the ETM only at 45 min post-injection, suggesting a rapid but not sustained anxiolytic-like effect. Altogether our results suggest that ketamine might have mixed effects in anxiety tests while it does not affect panic-related behaviors.HighlightsKetamine induces mixed effects in animal anxiety testsFew studies investigated the individual effects of S-ketamine in anxiety/fear testsNone study evaluated the effects of R-Ketamine on anxiety/fear-related behaviorsSystemic ketamine does not affect panic-like behaviors in the elevated T-maze

Effect of safranal, a constituent of crocus sativus, on MK-801-induced behavioral and memory deficits in rat

2011 ◽  
Vol 26 (S2) ◽  
pp. 1342-1342 ◽  
Author(s):  
E. Asadpour ◽  
H.R. Sadeghnia
Keyword(s):  
Spatial Memory ◽  
Memory Deficits ◽  
Nmda Receptor Antagonist ◽  
Behavioral Changes ◽  
Crocus Sativus ◽  
Psychotic Episode ◽  
Systemic Injection ◽  
Mk 801 ◽  
Average Reference ◽  
Male Wistar Rats

The psychotomimetic MK-801, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, induce behavioral and cognitive impairments similar to those seen in schizophrenia. Safranal, a constituent of Crocus sativus (saffron), was found to have anti-seizure and anti-ischemic effects. In the present study, we investigated the effect of safranal on behavioral changes and spatial memory deficits induced by MK-801 in adult male Wistar rats, using radial maze. Safranal (72.75, 145.5 and 291 mg/kg, i.p.) was administrated 30 min before MK-801 (5 mg/kg, i.p.). Single systemic injection of MK-801 significantly increased locomotion, stereotypic behavior (rearing, grooming, sniffing) and ataxia (p < 0.01) which became evident on day 1. Moreover, average reference and working memory errors were significantly increased within 10 days after MK-801 administration (p < 0.05).Pretreatment with safranal (291 mg/kg) significantly reduced locomotor hyperactivity and behavioral changes elicited by MK-801 (p < 0.001). Average reference errors were also significantly decreased in comparison with MK-801 treated animals (p < 0.01). These data indicated that treatment with safranal attenuated behavioral and spatial memory deficits in a rat model of an acute psychotic episode.

scholarly journals Ketamine Produces a Long-Lasting Enhancement of CA1 Neuron Excitability

2021 ◽  
Vol 22 (15) ◽  
pp. 8091
Author(s):  
Grace Jang ◽  
M. Bruce MacIver
Keyword(s):  
Nmda Receptor ◽  
Potassium Channel ◽  
Receptor Antagonist ◽  
Hippocampal Slices ◽  
Nmda Receptor Antagonist ◽  
Channel Block ◽  
Mk 801 ◽  
Ca1 Region ◽  
Excitatory Transmission ◽  
Ketamine Anesthesia

Ketamine is a clinical anesthetic and antidepressant. Although ketamine is a known NMDA receptor antagonist, the mechanisms contributing to antidepression are unclear. This present study examined the loci and duration of ketamine’s actions, and the involvement of NMDA receptors. Local field potentials were recorded from the CA1 region of mouse hippocampal slices. Ketamine was tested at antidepressant and anesthetic concentrations. Effects of NMDA receptor antagonists APV and MK-801, GABA receptor antagonist bicuculline, and a potassium channel blocker TEA were also studied. Ketamine decreased population spike amplitudes during application, but a long-lasting increase in amplitudes was seen during washout. Bicuculline reversed the acute effects of ketamine, but the washout increase was not altered. This long-term increase was statistically significant, sustained for >2 h, and involved postsynaptic mechanisms. A similar effect was produced by MK-801, but was only partially evident with APV, demonstrating the importance of the NMDA receptor ion channel block. TEA also produced a lasting excitability increase, indicating a possible involvement of potassium channel block. This is this first report of a long-lasting increase in excitability following ketamine exposure. These results support a growing literature that increased GABA inhibition contributes to ketamine anesthesia, while increased excitatory transmission contributes to its antidepressant effects.

scholarly journals GluN2B and GluN2A-containing NMDAR are differentially involved in extinction memory destabilization and restabilization during reconsolidation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andressa Radiske ◽  
Maria Carolina Gonzalez ◽  
Diana A. Nôga ◽  
Janine I. Rossato ◽  
Lia R. M. Bevilaqua ◽  
...  
Keyword(s):  
Inhibitory Avoidance ◽  
Receptor Subtypes ◽  
Memory Recall ◽  
Memory Retention ◽  
Local Protein Synthesis ◽  
Memory Recovery ◽  
Male Wistar Rats ◽  
Extinction Memory ◽  
The Moment ◽  
Local Protein

AbstractExtinction memory destabilized by recall is restabilized through mTOR-dependent reconsolidation in the hippocampus, but the upstream pathways controlling these processes remain unknown. Hippocampal NMDARs drive local protein synthesis via mTOR signaling and may control active memory maintenance. We found that in adult male Wistar rats, intra dorsal-CA1 administration of the non-subunit selective NMDAR antagonist AP5 or of the GluN2A subunit-containing NMDAR antagonist TCN201 after step down inhibitory avoidance (SDIA) extinction memory recall impaired extinction memory retention and caused SDIA memory recovery. On the contrary, pre-recall administration of AP5 or of the GluN2B subunit-containing NMDAR antagonist RO25-6981 had no effect on extinction memory recall or retention per se but hindered the recovery of the avoidance response induced by post-recall intra-CA1 infusion of the mTOR inhibitor rapamycin. Our results indicate that GluN2B-containing NMDARs are necessary for extinction memory destabilization whereas GluN2A-containing NMDARs are involved in its restabilization, and suggest that pharmacological modulation of the relative activation state of these receptor subtypes around the moment of extinction memory recall may regulate the dominance of extinction memory over the original memory trace.

NMDA Antagonist Peptide Supplementation Enhances Pain Alleviation by Adrenal Medullary Transplants

2005 ◽  
Vol 14 (4) ◽  
pp. 203-211 ◽  
Author(s):  
Farinaz Nasirinezhad ◽  
Jacqueline Sagen
Keyword(s):  
Neuropathic Pain ◽  
Animal Models ◽  
Striated Muscle ◽  
Thermal Hyperalgesia ◽  
Nmda Antagonist ◽  
Nmda Receptor Antagonist ◽  
Intraplantar Injection ◽  
Amino Acid Peptide ◽  
Spinal Subarachnoid Space ◽  
Pain Symptoms

Spinal transplantation of adrenal medullary chromaffin cells has been shown to decrease pain responses in several animal models. Improved potency may be possible by engineering cells to produce greater levels of naturally derived analgesics. As an initial screen for potential candidates, adrenal medullary transplants were evaluated in combination with exogenously administered neuropeptides in rodent pain models. Histogranin is a 15-amino acid peptide that exhibits NMDA receptor antagonist activity. The stable derivative [Ser1]histogranin (SHG) can attenuate pain symptoms in some animal models. The formalin model for neurogenic inflammatory pain and the chronic constriction injury (CCI) model for neuropathic pain were used to evaluate the combined effects of chromaffin cell transplantation and intrathecal (IT) SHG injections. Animals were implanted with either adrenal medullary or control striated muscle tissue in the spinal subarachnoid space. For evaluation of formalin responses, animals were pretreated with SHG (0.5, 1.0, 3.0 μg) followed by an intraplantar injection of formalin, and flinching responses were quantified. Pretreatment with SHG had no significant effect on flinching behavior in control animals at lower doses, with incomplete attenuation only at the highest dose. In contrast, 0.5 μg SHG significantly reduced flinching responses in animals with adrenal medullary transplants, and 1.0 μg nearly completely eliminated flinching in these animals in the tonic phase. For evaluation of effects on neuropathic pain, animals received transplants 1 week following CCI, and were tested for thermal and mechanical hyperalgesia and cold allodynia before and following SHG treatment. The addition of low doses of SHG nearly completely eliminated neuropathic pain symptoms in adrenal medullary transplanted animals, while in control transplanted animals only thermal hyperalgesia was attenuated, at the highest dose of SHG. These results suggest that SHG can augment adrenal medullary transplants, and the combination may result in improved effectiveness and range in the treatment of chronic pain syndromes.

scholarly journals Mechanism Underlying Protective Effect of MK-801 against NMDA-Induced Neuronal Injury in vivo

1991 ◽  
Vol 11 (5) ◽  
pp. 779-785 ◽  
Author(s):  
Daisuke Uematsu ◽  
Joel H. Greenberg ◽  
Nobuo Araki ◽  
Martin Reivich
Keyword(s):  
Neuronal Injury ◽  
Nmda Receptor Antagonist ◽  
Free Calcium ◽  
Protective Effects ◽  
Acetoxymethyl Ester ◽  
Initial Oxidation ◽  
Signal Ratio ◽  
Mk 801 ◽  
Sharp Waves

The effects of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the dihydropyridine calcium antagonist nimodipine on NMDA-induced phenomena were investigated using an in vivo fluorometric technique with indo-1. Indo-1, a fluorescent cytosolic free calcium ([Ca2+]i) indicator, was loaded into the cat cortex approximately 500 μm in depth by super-fusion with the membrane-permeant indo-1 acetoxymethyl ester (indo-1-AM). Changes in [Ca2+]i signals (400 and 506 nm) and reduced nicotinamide adenine dinucleotide (NADH) fluorescence (464 nm) were simultaneously measured directly from the cortex during ultraviolet excitation (340 nm). Superfusion of 100 μM NMDA over the exposed cortex induced an elevation of the [Ca2+]i signal ratio (400/506 nm), biphasic changes in NAD/NADH redox state (initial oxidation followed by progressive reduction), and characteristic changes in the EEG (abrupt depression in amplitude followed by an excitatory pattern of 18–22 Hz poly spikes or sharp waves). These changes were completely blocked by treatment with MK-801 and reduced by nimodipine. The mechanism underlying the protective effects of systemically administered MK-801 on the NMDA-induced neuronal injury was verified in vivo.

INTERACTION BETWEEN THE NONCOMPETITIVE NMDA ANTAGONIST MK-801 AND MORPHINE: EVALUATION BY AMBULATORY ACTIVITY IN MICE.

1992 ◽  
Vol 15 ◽  
pp. 635B
Author(s):  
Y. Iijima ◽  
T. Asami ◽  
H. Kuribara ◽  
I. Ida ◽  
T. Higuchi ◽  
...  
Keyword(s):  
Nmda Antagonist ◽  
Ambulatory Activity ◽  
Mk 801
Sign in / Sign up

Export Citation Format

Share Document