The N-methyl-d-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias

@article{Ellison1995TheNA,
  title={The N-methyl-d-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias},
  author={Gaylord D. Ellison},
  journal={Brain Research Reviews},
  year={1995},
  volume={20},
  pages={250-267}
}
  • G. Ellison
  • Published 1 February 1995
  • Psychology, Biology
  • Brain Research Reviews
View on Elsevier
doi.org
283 Citations
Highly Influential Citations
5
Background Citations
92
Methods Citations
6
Results Citations
4

283 Citations

Acute N-methyl-d-aspartate receptor hypofunction induced by MK801 evokes sex-specific changes in behaviors observed in open-field testing in adult male and proestrus female rats
NMDA Antagonist-Induced Neurotoxicity and Psychosis
TLDR
It became apparent that this class of drugs possessed the ability to produce both positive and negative symptoms of schizophrenia, which made NMDA antagonists a more complete animal model than dopamine agonists, the only other class of psychotomimetic drugs that induce only the positive Symptoms of schizophrenia.
Long-term changes in brain following continuous phencyclidine administration: an autoradiographic study using flunitrazepam, ketanserin, mazindol, quinuclidinyl benzilate, piperidyl-3,4-3H(N)-TCP, and AMPA receptor ligands.
TLDR
Autoradiographic studies using a variety of receptor ligands indicated enduring alterations in a number of receptors: these included decreased piperidyl-3,4-3H(N)-TCP (TCP), flunitrazepam, and mazindol binding in many of the limbic regions in which degeneration has been reported previously.
Repeated administration of phencyclidine, amphetamine and MK-801 selectively impairs spatial learning in mice: a possible model of psychotomimetic drug-induced cognitive deficits
TLDR
Five days of repeated PCP, AMPH or MK-801 administration selectively and differentially impaired the ability of mice to discriminate a spatial change, while leaving intact the ability to react to a non-spatial change, thus indicating that these regimens could also mimic some of the cognitive deficits observed in schizophrenia.
Neurotoxicity of dextrorphan.
Behavioral effects of chronic phencyclidine in monkeys.
TLDR
The results indicate that behavioral effects of chronic PCP in primates differ from those seen following acute treatments and represent an appropriate model system for new antipsychotic drug development.
Role of the NMDA receptor subunit in the expression of the discriminative stimulus effect induced by ketamine.
Chronic ketamine use and psychotic symptomatology
This thesis examines the effects of chronic use of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, on subjective experience and cognition. It is important to explore the…
Microinfusion of the non-competitive N-methyl-d-aspartate receptor antagonist MK-801 (dizocilpine) into the dorsal hippocampus of Wistar rats does not affect latent inhibition and prepulse inhibition, but increases startle reaction and locomotor activity
Effects on rat thalamic proteome by acute and subchronic MK-801-treatment.
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References

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MK-801, a proposed noncompetitive antagonist of excitatory amino acid neurotransmission, produces phencyclidine-like behavioral effects in pigeons, rats and rhesus monkeys.
TLDR
The findings of this study offer further support for the hypothesis that certain behavioral effects of PCP-like drugs may result from a reduction of neurotransmission at excitatory synapses utilizing NMDA-preferring receptors.
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These data indicate that N-methyl-D-aspartate antagonists produce a broad range of symptoms, behaviors, and cognitive deficits that resemble aspects of endogenous psychoses, particularly schizophrenia and dissociative states.
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It was found that PCP-induced psychotomimetic effects are associated with submicromolar serum concentrations of PCP and the findings suggest that endogenous dysfunction of NMDA receptor-mediated neurotransmission might contribute to the pathogenesis of schizophrenia.
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These findings raise new questions regarding the safety of these agents in the clinical management of neurodegenerative diseases and reinforce concerns about the potential risks associated with illicit use of PCP.
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  • Psychology, Biology
    Brain Research Reviews
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Differential effects of competitive and non-competitive N-methyl-d-aspartate antagonists on glucose use in the limbic system
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A case is here presented of long-term, high-dose ketamine use, in which the user described impaired recall and attention, and a subtle visual anomaly persisting after cessation of the habit.
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The results indicate that drugs of abuse with psychotomimetic properties induce distinctively different patterns of neural degeneration, a finding with implications for theories of addiction and psychosis.
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