Open AccessJournal Article
Characterization of MK-801-Induced Behavior as a Putative Rat Model of Psychosis
Peter Andiné,Nina Widermark,Rolf Axelsson,Gösta Nyberg,Ulla Olofsson,Erik Mårtensson,Mats Sandberg +6 more
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TLDR
MK-801-induced behavior represents a rat excitatory amino acid hypofunction model of psychosis that appears to be of clinical relevance and may be of value in the search for new antipsychotic agents.Abstract:
The objective of this study was to characterize the behavior induced by the N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine maleate) in rats as a model of psychosis. The temporal profile, dose dependence, age, and sex differences of the behavior are described. A gas chromatographic method for the analysis of MK-801 in plasma and brain was developed. Female rats showed 4 to 10 times more MK-801-induced behavior and displayed around 25 times higher serum and brain concentrations of MK-801 than male rats. Twenty-one neuroactive compounds, including a number of excitatory amino acid-active substances, were tested for the effect on MK-801-induced behavior. Neuroleptics blocked MK-801-induced behavior in a dose-dependent manner that correlated to their antipsychotic potency in humans. Adenosine receptor agonists and an N-methyl-D-aspartate receptor-associated glycine site antagonist showed putative antipsychotic effects. In conclusion, MK-801-induced behavior represents a rat excitatory amino acid hypofunction model of psychosis that appears to be of clinical relevance and may be of value in the search for new antipsychotic agents.read more
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Sex differences in animal models of psychiatric disorders.
Nikolaos Kokras,Christina Dalla +1 more
TL;DR: The need for the inclusion of both male and female animals in experimental studies aiming at gender‐oriented prevention, diagnosis and treatment of psychiatric disorders is highlighted.
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Chronic But Not Acute Treatment with a Metabotropic Glutamate 5 Receptor Antagonist Reverses the Akinetic Deficits in a Rat Model of Parkinsonism
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Effects of the cognition impairer MK-801 on learning and memory in mice and rats.
TL;DR: It is concluded that MK-801, administered into rodents in doses up to 0.1 mg kg(-1), appears to fulfill the criteria of a cognition impairer in rodents, without causing sensorimotor impairments and/or signs of intoxication.
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Long-term behavioural, molecular and morphological effects of neonatal NMDA receptor antagonism.
TL;DR: The data show that a transient and limited glutamatergic intervention during development can have chronic behavioural, structural and molecular effects, and are consistent with hypotheses advocating a role for NMDA receptor hypofunction, and aberrant apoptosis, in the neurodevelopmental pathogenesis of the disorder.
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Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: Psychotomimetic, perceptual, cognitive, and neuroendocrine responses.
John H. Krystal,Laurence P. Karper,John Seibyl,Glenna K. Freeman,Richard C. Delaney,J. Douglas Bremner,George R. Heninger,Malcolm B. Bowers,Dennis S. Charney +8 more
TL;DR: 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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Recent advances in the phencyclidine model of schizophrenia.
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Glutamate receptor dysfunction and schizophrenia.
John W. Olney,Nuri B. Farber +1 more
TL;DR: It is proposed that since N-methyl-D-aspartate receptor hypofunction can cause psychosis in humans and corticolimbic neurodegenerative changes in the rat brain, and since these changes are prevented by certain antipsychotic drugs, including atypical neuroleptic agents, a better understanding of this mechanism may lead to improved pharmacotherapy in schizophrenia.
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The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist.
Erik H. F. Wong,John A. Kemp,Tony Priestley,Antony R. Knight,Geoffrey Neil Woodruff,L. L. Iversen +5 more
TL;DR: Neurophysiological studies in vitro, using a rat cortical-slice preparation, demonstrated a potent, selective, and noncompetitive antagonistic action of MK-801 on depolarizing responses to N-Me-D-Asp but not to kainate or quisqualate, providing an explanation for the mechanism of action ofMK-801 as an anticonvulsant.