Critical involvement of the orbitofrontal cortex in hyperlocomotion induced by NMDA receptor blockade in mice

Seiriki, Kaoru; Kasai, Atsushi; Kuwaki, Takahiro; Nakazawa, Takahiro; Yamaguchi, Shun; Hashimoto, Hitoshi

doi:10.1016/j.bbrc.2016.10.089

Cited by 8 publications

(6 citation statements)

References 33 publications

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“…unpublished data). Furthermore, it has been reported that MK‐801 has a predominant effect on the orbitofrontal cortex (OFC), which is anatomically and molecularly altered upon loss of COUP‐TFI in the cortex, as previously shown . Thus, an abnormally organized OFC, critically involved in NMDA receptor‐mediated psychotic‐like behavioral abnormalities, such as hyperlocomotion, might be involved in the hyperactive behavior observed in COUP‐TFI mutant mice, and in some of the NR2F1 haploinsufficient patients.…”

Section: Discussionmentioning

confidence: 81%

Hyperactive and anxiolytic‐like behaviors result from loss of COUP‐TFI/Nr2f1 in the mouse cortex

Contesse

Ayrault

Mantegazza

et al. 2019

Genes Brain and Behavior

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The nuclear receptor COUP TFI (also known as Nr2f1) plays major roles in specifying distinct neuronal subtypes during patterning of the neocortical motor and somatosensory cortex, as well as in regulating the longitudinal growth of the hippocampus during development. In humans, mutations in the NR2F1 gene lead to a global developmental delay and intellectual disabilities. While more than 30% of patients show behavioral features of autism spectrum disorder, 16% of haploinsufficient children show signs of hyperactivity and impulsivity. Loss of COUP‐TFI in the cortical mouse primordium results in altered area organization and serotonin distribution, abnormal coordination of voluntary movements and learning and memory deficits. Here, we asked whether absence of COUP‐TFI affects locomotor activity, anxiety, as well as depression. Mice mutant for COUP‐TFI have normal motor coordination, but significant traits of hyperactivity, which does not seem to respond to N‐Methyl‐D‐aspartate (NMDA) antagonists. However, no changes in anxiety, despite increased locomotor performances, were observed in the open field task. On the contrary, elevated plus maze and dark‐light test explorations indicate a decreased anxiety‐like behavior in COUP‐TFI mutant mice. Finally, significantly reduced immobility in the forced swim test and no changes in anhedonia in the sucrose preference task suggest no particular depressive behaviors in mutant mice. Taken together, our study shows that loss of COUP‐TFI leads to increased locomotor activity but less anxiety and contributes in further deciphering the pathophysiology of patients haploinsufficient for NR2F1.

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Section: Discussionmentioning

confidence: 81%

Hyperactive and anxiolytic‐like behaviors result from loss of COUP‐TFI/Nr2f1 in the mouse cortex

Contesse

Ayrault

Mantegazza

et al. 2019

Genes Brain and Behavior

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“…Ketamine acts on NMDAR and results in NMDAR containing GABAergic interneuron hypofunction and subsequent pyramidal neuron hyperexcitability in the frontal cortex (Autry et al, ; Li et al, ; Nosyreva et al, ). MK‐801, another noncompetitive NMDAR antagonist, induced hyperlocomotion by elevating the frontal neuronal activity in the orbitofrontal area of mice (Seiriki et al, ). Schizophrenia was also mediated by frontal GABAergic activity through reduced NMDAR function (Cohen, Tsien, Goff, & Halassa, ).…”

Section: Discussionmentioning

confidence: 99%

Different FDG‐PET metabolic patterns of anti‐AMPAR and anti‐NMDAR encephalitis: Case report and literature review

Wei

Tseng

et al. 2020

Brain and Behavior

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Introduction 18F‐fluorodeoxyglucose (FDG)‐PET metabolic patterns of brain differ among autoimmune encephalitis with different neuronal surface antigens. In this case report, we compared the topographical relationship of cerebral glucose metabolism and antigen distribution in the patients with anti‐NMDAR and anti‐AMPAR encephalitis. Literature review summarized the common features of brain metabolism of autoimmune encephalitis. Methods The cerebral glucose metabolism was evaluated by FDG‐PET/CT during acute‐to‐subacute stage of autoimmune encephalitis and after treatment. The stereo and quantitative analysis of cerebral metabolism used standardized z‐score and visualized on three‐dimensional stereotactic surface projection. To map NMDAR and AMPAR in human brain, we adopted genetic atlases from the Allen Institute and protein atlases from Zilles's receptor densities. Results The three‐dimensional stereotactic surface projection displayed frontal‐dominant hypometabolism in a 66‐year‐old female patient with anti‐AMPAR encephalitis and occipital‐dominant hypometabolism in a 29‐year‐old female patient with anti‐NMDAR encephalitis. Receptor density maps revealed opposite frontal–occipital gradients of AMPAR and NMDAR, which reflect reduced metabolism in the correspondent encephalitis. FDG‐PET hypometabolic areas possibly represent receptor hypofunction with spatial correspondence to receptor distributions of the autoimmune encephalitis. The reversibility of hypometabolism was in line with patients' cognitive improvement. The literature review summarized six features of metabolic anomalies of autoimmune encephalitis: (a) temporal hypermetabolism, (b) frontal hypermetabolism and (c) occipital hypometabolism in anti‐NMDAR encephalitis, (d) hypometabolism in association cortices, (e) sparing of unimodal primary motor cortex, and (e) reversibility in recovery. Conclusions The distinct cerebral hypometabolic patterns of autoimmune encephalitis were representative for receptor hypofunction and topographical distribution of antigenic receptors. The reversibility of hypometabolism marked the clinical recovery of autoimmune encephalitis and made FDG‐PET of brain a valuable diagnostic tool.

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“…In line with this concept, uncompetitive NMDA receptor antagonists (including MK-801) increase glutamate release in this structure which via AMPA/kainate receptors excites pyramidal neurons, i.e. increases their metabolic activity, early gene expression, and firing [39][40][41][42][43][44].…”

Section: Discussionmentioning

confidence: 81%

Potential antipsychotic action of the selective agonist of adenosine A1 receptors, 5′-Cl-5′-deoxy-ENBA, in amphetamine and MK-801 rat models

2020

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Background Disturbances of dopaminergic and glutamatergic transmissions have been suggested to be involved in the pathomechanisms underlying psychotic symptoms of schizophrenia. In line with this concept, hyperlocomotion induced by the dopaminomimetic amphetamine and the uncompetitive antagonist of NMDA receptors MK-801 (dizocilpine) in rodents is a generally established model for screening of new potential antipsychotic drugs. Since recent studies have indicated that receptors for adenosine may be targets for antipsychotic therapy, the aim of the present study was to investigate an influence of 5′-Cl-5′-deoxy-ENBA, a potent and selective adenosine A 1 receptor agonist, on hyperlocomotion induced by amphetamine and MK-801. Methods Locomotor activity was measured by Force Plate Actimeters where four force transducers located below the corners of the floor of the cage tracked the animal position on a Cartesian plane at each time point. Results Hyperlocomotion induced by either amphetamine (1 mg/kg sc) or MK-801 (0.3 mg/kg ip) was inhibited by 5′-Cl-5′deoxy-ENBA (0.1 mg/kg ip). The effect of 5′-Cl-5′-deoxy-ENBA on the amphetamine-and MK-801-induced hyperlocomotion was antagonized by the selective antagonist of adenosine A 1 receptor DPCPX at doses of 1 and 2 mg/kg ip, respectively. Conclusion The present study suggests that stimulation of adenosine A 1 receptors may produce antipsychotic effects.

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Critical involvement of the orbitofrontal cortex in hyperlocomotion induced by NMDA receptor blockade in mice

Cited by 8 publications

References 33 publications

Hyperactive and anxiolytic‐like behaviors result from loss of COUP‐TFI/Nr2f1 in the mouse cortex

Hyperactive and anxiolytic‐like behaviors result from loss of COUP‐TFI/Nr2f1 in the mouse cortex

Different FDG‐PET metabolic patterns of anti‐AMPAR and anti‐NMDAR encephalitis: Case report and literature review

Potential antipsychotic action of the selective agonist of adenosine A1 receptors, 5′-Cl-5′-deoxy-ENBA, in amphetamine and MK-801 rat models

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