Ketamine-induced anesthesia involves the N-methyl-d-aspartate receptor-channel complex in mice

Irifune, Masahiro; Shimizu, Takao; Nomoto, Masahiro; Fukuda, Takeo

doi:10.1016/0006-8993(92)91525-j

Cited by 133 publications

(46 citation statements)

References 37 publications

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“…It could be argued that the absence of reorganization reported here was due to a synergistic interaction between our anesthetic regimen and the NMDA receptor blockade (eg., Anis et al, 1983;Irifune et al, 1992). Is it possible that the incomplete reorganization seen here arose from an additive effect of CPP and ketamine at what are normally relatively ineffective synapses?…”

Section: Consideration Of Possible Anesthesia-related Confoundsmentioning

confidence: 87%

NMDA receptors and plasticity in adult primate somatosensory cortex

1996

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Topographic maps in adult primate somatosensory cortex are capable of dramatic reorganizations after peripheral nerve injuries. In the present experiments, we have deprived a circumscribed portion of the hand map in somatosensory cortex of our adult squirrel monkeys by transecting the median nerve to one hand, and evaluated the hypothesis that N-methyl-d-aspartate (NMDA) glutamatergic receptors are necessary for the reorganization that follows within four weeks. In one monkey, we confirm previous results demonstrating that the deprived cortex has regained responsiveness in its expanse four weeks after median nerve transection. However, in three monkeys in which NMDA receptors were concurrently blocked, most of the deprived cortex remained unresponsive. Thus, much of the cortical "recovery" that typically follows peripheral nerve injury in adult monkeys is apparently dependent on NMDA receptors and may well be due to Hebbian-like changes in synaptic strength. Perhaps the elimination of the normally dominant inputs to "median nerve cortex" permits the gradual strengthening of correlations between the activity of the formally impotent presynaptic and deprived postsynaptic elements. These enhanced correlations may also have been made possible by reductions in intracortical inhibition as a necessary but not sufficient condition.

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Section: Consideration Of Possible Anesthesia-related Confoundsmentioning

confidence: 87%

NMDA receptors and plasticity in adult primate somatosensory cortex

1996

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“…The mechanisms by which anesthetic ketamine produces its adverse behavioral effects have been attributed, at least in part, to the blockade of the N-methyl-D-aspartate receptor 28 and to its agonistic properties on the ␥-aminobutyric acid type A receptor. 29,30 Furthermore, anesthetic ketamine inhibited both the ␣7 and the ␣4␤2 subunits of neural nicotinic acetylcholine receptors that are localized in the hippocampus and are implied in cognition.…”

Section: Discussionmentioning

confidence: 99%

Anesthetic Ketamine Impairs Rats' Recall of Previous Information

Boultadakis

Pitsikas

2011

Anesthesiology

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Background: There is poor experimental evidence concerning the effects of anesthetic doses of the noncompetitive N-methyl-D-aspartate receptor antagonist ketamine on rodents' memory abilities. The current study was designed (1) to investigate the consequences of posttraining administration of anesthetic ketamine (100 mg/kg intraperitoneally) on rats' recognition memory and (2) to evaluate the ability of the nitric oxide synthase inhibitor N-nitro-L-arginine methylester (L-NAME; 1, 3, and 10 mg/kg intraperitoneally) to counteract the expected behavioral deficits produced by anesthetic ketamine. Finally, in an attempt to clarify if the expected memory impairments produced by anesthetic ketamine were related to the anesthesia, we also tested the effects of a subanesthetic dose of it (3 mg/kg intraperitoneally) on rats' recognition memory. Methods: The novel object recognition test, a procedure assessing recognition memory in rats, was selected. Results: Posttraining administration of anesthetic (but not of subanesthetic) ketamine disrupted rats' performance in the novel object recognition paradigm. The discrimination index (D) was decreased by ketamine from 0.415 (using saline) to 0.128, thus indicating that the anesthetic dose of ketamine impaired recognition memory. L-NAME (1-3, but not 10, mg/ kg) reversed this memory deficit produced by ketamine; the D index of 0.128 using ketamine treatment was increased by 1 and 3 mg/kg L-NAME to 0.427 and 0.478, respectively.

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“…A number of studies also implicated GABA A receptors in ketamine anesthesia (Scholfield, 1980;Gage and Robertson, 1985;Bennett et al, 1988;Irifune et al, 1992Irifune et al, , 2000Lin et al, 1992;Wakasugi et al, 1999), although these provided either indirect evidence for the action of ketamine on GABA A receptors, or the concentration of ketamine used was significantly higher than the anesthetically relevant concentration.…”

Section: Introductionmentioning

confidence: 99%

Ketamine, But Not Phencyclidine, Selectively Modulates Cerebellar GABA_AReceptors Containing α6 and δ Subunits

Hevers¹,

Hadley²,

Lüddens³

et al. 2008

J. Neurosci.

121

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Phencyclidine (PCP) and ketamine are dissociative anesthetics capable of inducing analgesia, psychomimetic behavior, and a catatonic state of unconsciousness. Despite broad similarities, there are notable differences between the clinical actions of ketamine and PCP. Ketamine has a lower incidence of adverse effects and generally produces greater CNS depression than PCP. Both noncompetitively inhibit NMDA receptors, yet there is little evidence that these drugs affect GABA A receptors, the primary target of most anesthetics. ␣6␤2/3␦ receptors are subtypes of the GABA A receptor family and are abundantly expressed in granular neurons within the adult cerebellum. Here, using an oocyte expression system, we show that at anesthetically relevant concentrations, ketamine, but not PCP, modulates ␣6␤2␦ and ␣6␤3␦ receptors. Additionally, at higher concentrations, ketamine directly activates these GABA A receptors. Comparatively, dizocilpine (MK-801 [(ϩ)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate]), a potent noncompetitive antagonist of NMDA receptors that is structurally unrelated to PCP, did not produce any effect on ␣6␤2␦ receptors. Of the recombinant GABA A receptor subtypes examined (␣1␤2, ␣1␤2␥2, ␣1␤2␦, ␣4␤2␥2, ␣4␤2␦, ␣6␤2␥2, ␣6␤2␦, and ␣6␤3␦), the actions of ketamine were unique to ␣6␤2␦ and ␣6␤3␦ receptors. In dissociated granule neurons and cerebellar slice recordings, ketamine potentiated the GABAergic conductance arising from ␣6-containing GABA A receptors, whereas PCP showed no effect. Furthermore, ketamine potentiation was absent in cerebellar granule neurons from transgenic functionally null ␣6 ؊/؊ and ␦ ؊/؊ mice. These findings suggest that the higher CNS depressant level achieved by ketamine may be the result of its selective actions on ␣6␤2/3␦ receptors.

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Ketamine-induced anesthesia involves the N-methyl-d-aspartate receptor-channel complex in mice

Cited by 133 publications

References 37 publications

NMDA receptors and plasticity in adult primate somatosensory cortex

NMDA receptors and plasticity in adult primate somatosensory cortex

Anesthetic Ketamine Impairs Rats' Recall of Previous Information

Ketamine, But Not Phencyclidine, Selectively Modulates Cerebellar GABA_AReceptors Containing α6 and δ Subunits

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Ketamine-induced anesthesia involves the N-methyl-d-aspartate receptor-channel complex in mice

Cited by 133 publications

References 37 publications

NMDA receptors and plasticity in adult primate somatosensory cortex

NMDA receptors and plasticity in adult primate somatosensory cortex

Anesthetic Ketamine Impairs Rats' Recall of Previous Information

Ketamine, But Not Phencyclidine, Selectively Modulates Cerebellar GABAAReceptors Containing α6 and δ Subunits

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Ketamine, But Not Phencyclidine, Selectively Modulates Cerebellar GABA_AReceptors Containing α6 and δ Subunits