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

In acute brain injury syndromes, the potent N-methyl-D-aspartate (NMDA) antagonist, MK-801, can prevent neuronal degeneration, and the general anesthetics, isoflurane and propofol, may also provide neuroprotective benefits. An obstacle to the use of NMDA antagonists for neuroprotective purposes is that they can cause a neurotoxic vacuole reaction in cerebrocortical neurons. This study demonstrates the ability of isoflurane and propofol to prevent the neurotoxic vacuole reaction induced by MK-801. Low sedative doses of inhaled isoflurane (1%) or intravenous (i.v.) propofol (7.5 mg/kg/h) were as effective as higher general anesthetic doses. Thus, in the clinical management of acute brain injury conditions such as stroke and brain trauma, administration of one of these anesthetic agents together with an NMDA antagonist may be an excellent formula for obtaining optimal neuroprotection while eliminating serious side effects.

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

10.1101/793398 ◽

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

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Spectral analysis of the electroencephalogram in neonatal rats chronically treated with the NMDA antagonist MK-801

Developmental Brain Research ◽

10.1016/0165-3806(91)90206-x ◽

1991 ◽

Vol 64 (1-2) ◽

pp. 37-41 ◽

Cited By ~ 17

Author(s):

Jan A. Gorter ◽

Monica Veerman ◽

Majid Mirmiran ◽

Nico P.A. Bos ◽

Michael A. Corner

Keyword(s):

Spectral Analysis ◽

Nmda Antagonist ◽

Neonatal Rats ◽

Mk 801

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Role of NMDA and AMPA glutamatergic transmission in spinal c-fos expression after urinary tract irritation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.270.5.r990 ◽

1996 ◽

Vol 270 (5) ◽

pp. R990-R996 ◽

Cited By ~ 9

Author(s):

H. Kakizaki ◽

M. Yoshiyama ◽

W. C. de Groat

Keyword(s):

Spinal Cord ◽

Urinary Tract ◽

Nmda Antagonist ◽

Early Gene ◽

Mk 801 ◽

Sacral Parasympathetic Nucleus ◽

Fos Expression ◽

Dose Dependent Decrease ◽

Nociceptive Input

Chemical irritation of the lower urinary tract (LUT) of the rat increases the expression of the immediate early gene c-fos within neurons in the dorsal horn (DH), dorsal commissure (DCM), and intermediolateral region, including sacral parasympathetic nucleus (SPN) of the spinal cord (L6-S1). A previous study indicated the involvement of the N-methyl-D-aspartic acid (NMDA) receptor in this c-fos expression after LUT irritation. The role of glutamatergic synapses was further investigated using a selective and competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist (LY-215490). Systemic administration of LY-215490 produced a dose-dependent decrease in the number of Fos-positive cells after LUT irritation in the DCM and SPN areas, whereas in the DH only the highest dose (10 mg/kg) of LY-215490 decreased the number of Fos-positive cells. A low dose (1 mg/kg) of either MK-801 (an NMDA antagonist) or LY-215490 alone did not alter c-fos expression. However, a combined administration of low doses of MK-801 and LY-215490 significantly decreased the number of Fos-positive cells in all regions of the spinal cord. These results indicate that AMPA as well as NMDA receptors are involved in the spinal processing of nociceptive input from the LUT and that these glutamatergic receptors play a synergistic role in visceral nociceptive processing.

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