Topic: MK-801

The fundamental assumption of a functional system for encoding spatial information lies in the stability and preserved integrity of neural representations. In extreme cases, such as psychotic states in schizophrenia, there is a disruption of this stability, often resulting in the fusion of distinct neural representations. In this study, both familiar (F) and novel (N) linear mazes were utilized to assess the quality of neural coding across various time scales in 3-6 months old rats (N = 12). Lower (0.1 mg/kg) and higher doses (0.15 mg/kg) of MK-801 were administered. We observed disrupted spat

Aims: This study aims to elucidate the transcriptomic changes underlying thalamic alterations in an animal model of schizophrenia. Methods: We used a 'dual hit' rat model of schizophrenia, which combines an injection of non-competitive NMDA receptor antagonist MK-801 at P7 and 8 weeks of postweaning social isolation. The model was developed in both male and female rats. At 3 months, behavioral tests and RNA sequencing (RNAseq) of the thalamus were performed. Differential expressed genes (DEGs) and enriched categories were validated in silico via MAGMA using GWAS summary statistics of the Psych

While current antidepressants tackle depressive symptoms, they often fall short in addressing cognitive deficits associated with depression. Expanding upon our previous study on HBK-10, a multimodal compound targeting 5-HT1A receptors and demonstrating antidepressant-like properties, we now aim to investigate its procognitive potential and the underlaying mechanisms.First, we evaluated the influence of HBK-10 on ß-arrestin recruitment using CHO-K1 cells expressing the 5-HT1Areceptor. Subsequently, we conducted the Morris water maze test, employing the NMDA receptor antagonist MK-801 to induce

Mental disorders, including depression and anxiety, are a major health concern worldwide, affecting more than 540 million people globally. Although there are treatments available to help with various symptoms, cognitive deficits, particularly impaired executive functions, are often not addressed. In this study, we aim to investigate the effectiveness of HBK-15, a multimodal compound known for its rapid antidepressant-like effect, in reducing cognitive flexibility deficits in mice.We used male Balb/c mice. To assess the effect on cognitive flexibility, we used touchscreen-based two-choice pairw

Depression affects 30 million people worldwide, and women are diagnosed with this condition nearly twice as often as men. Cognitive impairments that develop during depression contribute to poor therapeutic outcomes and reduced quality of life. Recognizing the significance of sex as a variable in depression research, we investigated the procognitive properties of a multimodal compound- HBK-15 in female mice using two models of cognitive impairments: induced by NMDA receptor blockade or stress. We employed the object recognition test to assess intermediate recognition memory. We used MK-801 (NMD

The NEGR1 (neuronal growth regulator 1) gene has been associated with schizophrenia phenotype in GWAS studies and its expression has been found to be altered in the brains of patients with schizophrenia spectrum disorders. As altered profile of circulating kynurenine pathway metabolites has been linked with schizophrenia spectrum disorders as well, we aimed to find the differences in the brain and blood serum metabolite levels between wild-type mice and Negr1-deficient mice using MK-801 (dizocilpine) and a high-fat diet. The results suggest that kynurenine metabolism is strongly biased towards

Depression is a serious mental illness that includes both behavioral symptoms and cognitive dysfunction. With the growing problem of ineffective treatment, there is a constant need for compounds with rapid antidepressant and procognitive effects. A compound that has shown antidepressant-like activity after single administration in animal models is NLX-101. NLX-101 preferentially activates postsynaptic 5-HT1A heteroreceptors in the prefrontal cortex, stimulating extracellular signal-regulated kinase (ERK1/2) phosphorylation. Thus, this study aimed to evaluate the potential ability of NLX-101 to

In this study we have investigated the plasticity-related changes observed in the medial prefrontal cortex (mPFC) of a dual-hit model of schizophrenia developed in rats. The dual-hit model combines an injection of non-competitive NMDA receptor antagonist MK-801 at P7 and 8 weeks of postweaning social isolation. The model was developed in both male and female rats. At P90 RNA sequencing (RNAseq) was conducted on the prefrontal cortex. Differential expressed genes (DEGs) and enriched categories were validated in silico via MAGMA using GWAS summary statistics of the Psychiatric Genomics Consortiu

N-methyl-D-aspartate receptors (NMDARs) are a family of ionotropic glutamate receptors that mediate excitatory neurotransmission in the CNS. Native NMDARs are assembled as heterotetramers composed of two obligatory GluN1 and two GluN2A-D/GluN3A-B subunits at various combinations. The opening of the ion channel is a central feature of NMDAR function and is controlled by binding of two co-agonists (glutamate/glycine) to the agonist binding domains (ABD). In our previous work, using molecular dynamics simulations, we proposed functionally important residues in this process of channel opening, Glu

Alzheimer's disease (AD) is characterized by a dramatic loss of old consolidated memory. Our study proposes a new hypothesis that neurodegeneration affects mechanisms of memory reconsolidation, leading to the weakening of old memories when they are retrieved in the diseased brain, resulting in gradual self-degradation of the consolidated memory. Testing this hypothesis in transgenic 5xFAD mice we found that their contextual memory was impaired following retrieval compared to control animals. To protect memory during reconsolidation, we administered the NMDA receptor antagonist MK-801 which is