NMDA Receptor Antagonism and Cognitive Impairment in Schizophrenia Models
Summary
NMDA receptor antagonism is widely employed to model the glutamatergic hypofunction believed to underlie cognitive deficits in schizophrenia. Non-competitive antagonists such as MK-801 and phencyclidine induce a spectrum of schizophrenia-like symptoms in rodents and other organisms, notably impairments in working memory, behavioural flexibility, attentional set-shifting and sensorimotor gating. These models have illuminated the role of disrupted synaptic plasticity, reduced inhibitory interneuron function—particularly parvalbumin-expressing cells—and altered neurotrophic support, including downregulation of brain-derived neurotrophic factor, in prefrontal cortex and hippocampus. Cognitive tasks such as the Morris water maze, novel object recognition, set-shifting paradigms and prepulse inhibition assess distinct domains of executive function and memory. Translational relevance has been strengthened by convergent evidence that glutamatergic modulation and restoration of NMDA-dependent signalling can ameliorate such deficits, guiding the search for procognitive therapeutics. The global significance of these models is underscored by their value in dissecting circuit-level mechanisms of cognitive impairment and in preclinical screening of novel antipsychotic compounds targeting glutamate, GABA and neurotrophic pathways.
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NMDA Receptor Antagonism and Cognitive Impairment in Schizophrenia Models publication trend
The graph below shows the total number of articles in nmda receptor antagonism and cognitive impairment in schizophrenia models across all publications each year (not limited to Nature Index journals).
Technical terms
NMDA receptor: A subtype of glutamate receptor critical for synaptic plasticity and memory formation.
Parvalbumin interneurons: Fast-spiking GABAergic cells essential for cortical synchrony and cognitive processing.
Brain-derived neurotrophic factor (BDNF): A neurotrophin that supports neuronal survival, differentiation and synaptic strength.
Set-shifting: The ability to switch behavioural strategies in response to changing rules or stimuli.
Prepulse inhibition: A measure of sensorimotor gating in which a weak pre-stimulus reduces the reaction to a subsequent startling stimulus.
References
- Particulate matter (PM10) exacerbates on MK-801-induced schizophrenia-like behaviors through the inhibition of ERK-CREB-BDNF signaling pathway. Ecotoxicology and Environmental Safety (2024).
- MK-801 and cognitive functions: Investigating the behavioral effects of a non-competitive NMDA receptor antagonist. Psychopharmacology (2023).
- Repeated Blockade of NMDA Receptors During Adolescence Impairs Reversal Learning and Disrupts GABAergic Interneurons in Rat Medial Prefrontal Cortex. Frontiers in Molecular Neuroscience (2016).
- Postnatal BDNF Expression Profiles in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by MK‐801 Administration. BioMed Research International (2010).
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