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
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.
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.
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
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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
    The International journal of the addictions
  • 1990
TLDR
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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