Journal ArticleDOI
MK-801-induced stereotypy and its antagonism by neuroleptic drugs.
TLDR
Stereotypy is considered to represent an animal model of schizophrenia, and the antagonism of stereotypy with classical (haloperidol) as well as with atypical (clozapine) antipsychotic drugs is in accordance with the glutamate hypothesis of schizophrenia.Abstract:
MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo-(a,d)cyclo-hepten-5, 10-imine hydrogen maleate], which blocks glutamatergic transmission at the NMDA-receptor-gated ion chanel, induced stereotypies which are similar to those found after intrastriatal injections of AP-5, e.g. sniffing and locomotion. Tests in familiar or unfamiliar environment (non-stressful or stressful situation) did not qualitatively change MK-801-induced effects. Haloperidol (0.1mg/kg, IP) delayed the onset and shortened the duration of MK-801 (0.16; 0.33mg/ kg, IP)-induced stereotypy whereas clozapine (5 mg/kg, SC) potently antagonized it. However, exact quantification of sniffing, measured in an experimental chamber designed for this purpose, revealed an antagonism by both drugs, haloperidol as well as clozapine. Stereotypy is considered to represent an animal model of schizophrenia, and the antagonism of stereotypy with classical (haloperidol) as well as with atypical (clozapine) antipsychotic drugs is in accordance with the glutamate hypothesis of schizophrenia.read more
Citations
More filters
Journal ArticleDOI
Synaptic plasticity and memory: an evaluation of the hypothesis
TL;DR: It is concluded that a wealth of data support the notion that synaptic plasticity is necessary for learning and memory, but that little data currently supports the notion of sufficiency.
Journal ArticleDOI
Antipsychotic agents antagonize non-competitive N-methyl-D-aspartate antagonist-induced behaviors.
TL;DR: Assessment of the effects of antipsychotic agents in the CMA, MK-801-LF and PCP-induced social withdrawal assays may provide a preclinical approach to identify novel agents for negative symptoms and treatment resistant schizophrenia.
Journal 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
TL;DR: 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.
Journal ArticleDOI
NCS-1 in the Dentate Gyrus Promotes Exploration, Synaptic Plasticity, and Rapid Acquisition of Spatial Memory
Bechara J. Saab,John Georgiou,Arup Nath,Frank J.S. Lee,Min Wang,Aubin Michalon,Fang Liu,Isabelle M. Mansuy,John C. Roder,John C. Roder +9 more
TL;DR: A role for NCS-1 and D2R in DG plasticity is demonstrated and insight is provided for understanding how the DG contributes to the origin of exploration and spatial memory acquisition.
Journal ArticleDOI
An integrated view of pathophysiological models of schizophrenia.
TL;DR: A confluence of clinical and basic science data suggests that an early developmental insult, potentially involving reduced NMDA receptor function, could facilitate sensitization of dopamine systems, leading to the formal onset of schizophrenia in late adolescence and early adulthood.
References
More filters
Journal ArticleDOI
Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum.
TL;DR: Recovery of behavioural effects correlated with an increase in the remaining levels of DA in the NAS, and there is evidence that remaining DA levels in theNAS are greater at 90 than at 14 days postoperatively.
Journal ArticleDOI
Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia
TL;DR: Preliminary evidence indicates that this reduced glutamate content is not due to neuroleptic treatment, and is interpreted by the hypothesis that there is a dysfunction or degeneration of glutamatergic neurons in schizophrenia.
Journal ArticleDOI
Central sympathomimetic activity of (+)-5-methyl-10, 11-dihydro-5H-dibenzo [a, d] cyclohepten-5, 10-imine(MK-801), a substance with potent anticonvulsant, central sympathomimetic and apparent anxiolytic properties
TL;DR: Besides being a potent anticonvulsant, MK‐801 demonstrated selectivity, since much higher doses were required in mice to block clonic convulsions produced by pentylenetetrazol and tonic seizures caused by strychnine than were needed against electroshock or bicuculline.
Journal ArticleDOI
The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice
Maria L. Carlsson,Arvid Carlsson +1 more
TL;DR: It was shown that the selective non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 caused a pronounced and dose-dependent increase in locomotion in mice pretreated with a combination of reserpine and α- methyl-para-tyrosine.
Journal Article
MK-801, a proposed noncompetitive antagonist of excitatory amino acid neurotransmission, produces phencyclidine-like behavioral effects in pigeons, rats and rhesus monkeys.
TL;DR: 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.
Related Papers (5)
The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice
Maria L. Carlsson,Arvid Carlsson +1 more
Interactions between glutamatergic and monoaminergic systems within the basal ganglia-implications for schizophrenia and Parkinson's disease
Maria L. Carlsson,Arvid Carlsson +1 more