scholarly journals Modulating amygdala activation to traumatic memories with a single ketamine infusion

2021 ◽  
Author(s):  
Or Duek ◽  
Yutong Li ◽  
Benjamin Kelmendi ◽  
Shelley Amen ◽  
Charles Gordon ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptor Antagonist ◽  
Vital Role ◽  
Nmda Receptor Antagonists ◽  
Fear Response ◽  
Traumatic Memories ◽  
Trauma Memory ◽  
Amygdala Activity ◽  
Altered Form ◽  
Labile State

NMDA receptor antagonists have a vital role in extinction, learning, and reconsolidation processes. During the reconsolidation window, memories are activated into a labile state and can be stored in an altered form. This concept might have significant clinical implications in treating PTSD. Using amygdala activity as a major biomarker of fear response, we tested the potential of a single subanesthetic intravenous infusion of ketamine (NMDA receptor antagonist) to enhance post-retrieval extinction of PTSD trauma memories. Post-extinction, ketamine recipients (vs midazolam) showed a lower amygdala and hippocampus reactivation to trauma memories. Post-retrieval ketamine administration was also associated with decreased connectivity between the amygdala and hippocampus, with no change in amygdala-vmPFC connectivity, which suggests that ketamine may enhance post-retrieval extinction of PTSD trauma memory in humans. These findings demonstrate the capacity to rewrite human traumatic memories and to modulate the fear response for at least 30 days post-extinction.

scholarly journals Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

2011 ◽  
Vol 301 (2) ◽  
pp. R448-R455 ◽  
Author(s):  
Jason Wright ◽  
Carlos Campos ◽  
Thiebaut Herzog ◽  
Mihai Covasa ◽  
Krzysztof Czaja ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Fourth Ventricle ◽  
Nmda Receptor Antagonist ◽  
Behavioral Pattern ◽  
Vagal Afferents ◽  
Nmda Receptor Antagonists ◽  
The Brain

Intraperitoneal injection of CCK reduces food intake and triggers a behavioral pattern similar to natural satiation. Reduction of food intake by CCK is mediated by vagal afferents that innervate the stomach and small intestine. These afferents synapse in the hindbrain nucleus of the solitary tract (NTS) where gastrointestinal satiation signals are processed. Previously, we demonstrated that intraperitoneal (IP) administration of either competitive or noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists attenuates reduction of food intake by CCK. However, because vagal afferents themselves express NMDA receptors at both central and peripheral endings, our results did not speak to the question of whether NMDA receptors in the brain play an essential role in reduction of feeding by CCK. We hypothesized that activation of NMDA receptors in the NTS is necessary for reduction of food intake by CCK. To test this hypothesis, we measured food intake following IP CCK, subsequent to NMDA receptor antagonist injections into the fourth ventricle, directly into the NTS or subcutaneously. We found that either fourth-ventricle or NTS injection of the noncompetitive NMDA receptor antagonist MK-801 was sufficient to inhibit CCK-induced reduction of feeding, while the same antagonist doses injected subcutaneously did not. Similarly fourth ventricle injection of d-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphoric acid (d-CPPene), a competitive NMDA receptor antagonist, also blocked reduction of food intake following IP CCK. Finally, d-CPPene injected into the fourth ventricle attenuated CCK-induced expression of nuclear c-Fos immunoreactivity in the dorsal vagal complex. We conclude that activation of NMDA receptors in the hindbrain is necessary for the reduction of food intake by CCK. Hindbrain NMDA receptors could comprise a critical avenue for control and modulation of satiation signals to influence food intake and energy balance.

Lack of Effect of Intrathecally Administered N-methyl-D-aspartate Receptor Antagonists in a Rat Model for Postoperative Pain 

1998 ◽  
Vol 88 (1) ◽  
pp. 143-156 ◽  
Author(s):  
Peter K. Zahn ◽  
Timothy J. Brennan
Keyword(s):  
Nmda Receptor ◽  
Postoperative Pain ◽  
Rat Model ◽  
Intrathecal Administration ◽  
Nmda Receptor Antagonist ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists ◽  
Mk 801 ◽  
Pain Behaviors ◽  
Plantar Incision

Background Evidence from experiments by others indicates an important role for excitatory amino acids activating spinal n-methyl-d-aspartate (NMDA) receptors in models of persistent pain. The purpose of this study was to examine the effect of intrathecal (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine (MK-801), a noncompetitive NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (AP5), a competitive NMDA receptor antagonist, and N-G-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on pain behaviors in a rat model of postoperative pain. Methods Rats with intrathecal catheters were anesthetized and underwent a plantar incision. Withdrawal threshold to punctate stimulation applied adjacent to the wound, response frequency to application of a nonpunctate stimulus applied directly to the wound, and nonevoked pain behaviors were measured before and after intrathecal administration of MK-801 or AP5. The effect of intrathecal L-NAME on mechanical hyperalgesia was also examined. Results Mechanical hyperalgesia increased and was persistent after plantar incision and was not decreased by intrathecal administration of 4, 14, or 40 nmol MK-801 or 10 nmol AP5. Only the greatest dose of AP5, 30 nmol, caused a small decrease in punctate and nonpunctate hyperalgesia. Intrathecal L-NAME had no effect. Neither intrathecal MK-801 nor intrathecal AP5 affected nonevoked pain behaviors. The greatest doses caused motor deficits. Conclusions Unlike intrathecal and systemic morphine, intrathecal NMDA receptor antagonists did not modify pain behaviors in this rat model of postoperative pain. These data suggest that NMDA receptors do not play an important role in the maintenance of postoperative pain behaviors and that NMDA receptor antagonists, administered spinally by themselves during the postoperative period, will not be useful for the treatment of postoperative pain in humans.

Review of synthetic approaches to dizocilpine

2020 ◽  
Vol 24 ◽  
Author(s):  
Jan Konecny ◽  
Eva Mezeiova ◽  
Ondrej Soukup ◽  
Jan Korabecny
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Neuronal Plasticity ◽  
Nmda Receptor Antagonist ◽  
Human Medicine ◽  
Ionotropic Glutamate Receptors ◽  
Nmda Receptor Antagonists ◽  
Nmda Antagonists ◽  
The Family ◽  
Synthetic Approaches

Abstract:: N-Methyl-D-aspartate (NMDA) receptors together with AMPA and kainite receptors belongs to the family of ionotropic glutamate receptors. NMDA receptors plays a crucial role in neuronal plasticity and cognitive functions. Overactivation of those receptors leads to glutamate induced excitotoxicity, which could be suppressed by NMDA antagonists. Dizocilpine was firstly reported in 1982 as a NMDA receptor antagonist with anticonvulsive properties, but due to serious side effects like neuronal vacuolization, its use in human medicine is restricted. However, dizocilpine is still used as validated tool to induce the symptoms of schizophrenia in animal models and also as a standart for comparative purposes to newly developed NMDA receptor antagonists. For this reason, synthesis of dizocilpine and specially its more active enantiomer (+)-dizocilpine is still relevant. In this review we bring a collection of various synthetic approaches leading to dizocilpine and its analogues.

Ketamine and other NMDA receptor antagonists

2010 ◽  
pp. 115-124
Author(s):  
Marie Fallon ◽  
Cameron Fergus ◽  
Barry J.A. Laird
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists ◽  
Oral Ketamine ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

Ketamine is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist and is most effective in pain states where hyper-excitability is established Ketamine undergoes first-pass metabolism to norketamine, which is a more potent analgesic than ketamine. This can explain why oral ketamine is more potent than parenteral ketamine...

Sign in / Sign up

Export Citation Format

Share Document