The effect of neonatal N-methyl-d-aspartate receptor blockade on exploratory and anxiety-like behaviors in adult BALB/c and C57BL/6 mice

Akıllıoğlu, Kübra; Binokay, Seçil; Kocahan, Sayad

doi:10.1016/j.bbr.2012.04.041

Cited by 21 publications

(10 citation statements)

References 41 publications

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“…It is reported that treatment with NMDA receptor antagonists during early developmental stages leads to an increase both in locomotor activity and exploratory behaviors [18][19][20]; however, in our study there was a decrease in the locomotor activity and exploratory behaviors. Our previous study also showed decreases in adult locomotor activity and exploratory behavior [21,22]. Studies report that there are continuous interactions between the dopaminergic and the NMDA pathways.…”

Section: Discussionsupporting

confidence: 55%

Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801

Pınar

Akıllıoğlu

Sefil

et al. 2015

Bosn J of Basic Med Sci

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Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (p<0.05), while the open-field test indicated a decrease in locomotor activity (p<0.01). Despite these reductions, clozapine could not reverse the NMDA receptor blockade. Also, as an atypical antipsychotic agent, clozapine could not reverse impairment in the locomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period.

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Section: Discussionsupporting

confidence: 55%

Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801

Pınar

Akıllıoğlu

Sefil

et al. 2015

Bosn J of Basic Med Sci

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“…OFT was adopted to access the exploratory behaviors and emotional disorders including anxiety-like and depression-like behaviors 19,20 , whilst an automated three-chambered social approach task was used for evaluating sociability 21 . Our results are in agreement with studies showing that administration of MK801 to neonatal animals induced reduction in spontaneous locomotor activity in long-term which may re ect psychomotor retardation 22,23,24 . For example, a consecutive 5-day administration of MK801 in neonatal Balb/c mice (P7) produced a negative model of schizophrenia including hypoactivity in OFT 22 .…”

Section: Discussionsupporting

confidence: 93%

“…Our results are in agreement with studies showing that administration of MK801 to neonatal animals induced reduction in spontaneous locomotor activity in long-term which may re ect psychomotor retardation 22,23,24 . For example, a consecutive 5-day administration of MK801 in neonatal Balb/c mice (P7) produced a negative model of schizophrenia including hypoactivity in OFT 22 .…”

Section: Discussionsupporting

confidence: 93%

“…In summary, present study further substantiated the nding that MK801 administration to neonatal mice could induce a negative model of schizophrenia 43,44,45 . Speci cally 22,23,31 , a consecutive 5-day administration protocol of MK801 in neonatal mice (P7) induced negative symptoms of schizophrenia including hypoactivity and less sociability. These abnormalities could be explained by changes to NMDA receptor subtypes and GABAergic neurotransmitter, and the consequential excitatory/inhibitory neurotransmission imbalance in the pyramidal neurons in laminar II-III of the PFC.…”

Section: Discussionmentioning

confidence: 99%

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Low-concentration sevoflurane inhalation in treating MK801-induced schizophrenia like disease in mice and a feasibility study of schizophrenia patients

Zhao¹,

Shi²,

Ling³

et al. 2020

Preprint

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GABAergic deficits have been considered to associate with the pathophysiology of schizophrenia and hence GABA receptor subtype A (GABAARs) modulators may have therapeutic values for schizophrenia. Sevoflurane, a commonly used volatile anesthetic, enhances GABAergic neurotransmission through the GABAAR. The present study aims to investigate the therapeutic effectiveness of low-concentration sevoflurane in MK801-induced schizophrenia-like mice and amongst schizophrenia patients in a single arm trial. Three weeks after administration of MK801 (0.5 mg/kg, i.p. twice a day) for five days, mice were exposed to 1% sevoflurane for 1 hr/day for 5 days. One week after treatment, they were subjected to behavioral tests, and then sacrificed for immunohistochemical stain, western blot assay and electrophysiology recordings in the prefrontal cortex. Ten schizophrenia patients received 5-hr sevoflurane (0.5–1.2%) for 6 days, and were assessed with the PANSS and the BPRS-18 in the 1st and 2nd week after the treatments. MK801 induced hypolocomotion and social deficits, downregulated the expression of NMDARs subunits, and postsynaptic density protein 95 (PSD95), reduced parvalbumin- and GAD67-positive neurons, and changed the amplitude and frequency of mEPSC and mIPSC and evenly increased the excitation/inhibition (E/I) ratio. All these changes induced by MK-801 were attenuated by sevoflurane administration. Schizophrenia symptoms assessed with the scales were significantly improved in the 1st and 2nd week after treatments. Low-concentration sevoflurane inhalation effectively reversed MK801-induced schizophrenia-like disease in mice and alleviated schizophrenia patients’ symptoms. Our work suggested that sevoflurane may be a valuable therapeutic strategy for treating schizophrenia patients.

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“…However, whereas both increased wall-hugging and increased bottom-dwell time during the first few minutes in an unfamiliar environment are well-described neophobic responses (which habituate within about 5 min and are susceptible to anxiolytic drugs) in zebrafish, those behaviors are not necessarily unequivocal signs of anxiety, especially not in a 20-min experiment (for further discussion see [15], [36]). Whether MK-801 increases or decreases anxiety is not solved (for zebrafish [31], for mice [47]). Based on the literature, at least two alternative explanations for the altered (horizontal and vertical) spatial distribution patterns have to be considered: (1) spatial disorientation as might be indicated by poor spatial memory performance in zebrafish treated with MK-801 [30] and (2) increased occurrence of restrictive repetitive behaviors (which is one of the diagnostic criteria for ASD [48]) as is indicated by increased circling behavior in both mice [23] and zebrafish [32] and increased erratic movements in zebrafish [31] treated with the drug.…”

Section: Discussionmentioning

confidence: 99%

Assessing Social Engagement in Heterogeneous Groups of Zebrafish: A New Paradigm for Autism-Like Behavioral Responses

Maaswinkel¹,

Zhu²,

Weng³

2013

PLoS ONE

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Because of its highly developed social character, zebrafish is a promising model system for the study of the genetic and neurochemical basis of altered social engagement such as is common in autism and schizophrenia. The traditional shoaling paradigm investigates social cohesion in homogeneous groups of zebrafish. However, the social dynamics of mixed groups is gaining interest from a therapeutic point of view and thus warrants animal modeling. Furthermore, mutant zebrafish are not always available in large numbers. Therefore, we developed a new paradigm that allows exploring shoaling in heterogeneous groups. The effects of MK-801, a non-competitive antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor, on social cohesion were studied to evaluate the paradigm. The drug has previously been shown to mimic aspects of autism and schizophrenia. Our results show that a single MK-801-treated zebrafish reduced social cohesion of the entire shoal drastically. Preliminary observations suggest that the social dynamics of the shoal as a whole was altered.

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The effect of neonatal N-methyl-d-aspartate receptor blockade on exploratory and anxiety-like behaviors in adult BALB/c and C57BL/6 mice

Cited by 21 publications

References 41 publications

Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801

Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801

Low-concentration sevoflurane inhalation in treating MK801-induced schizophrenia like disease in mice and a feasibility study of schizophrenia patients

Assessing Social Engagement in Heterogeneous Groups of Zebrafish: A New Paradigm for Autism-Like Behavioral Responses

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