The effect of non-competitive NMDA receptor antagonist MK-801 on neuronal activity in rodent prefrontal cortex: an animal model for cognitive symptoms of schizophrenia

• MK-801 induces lasting potentiation of hippocampo-prefrontal cortex responses.
• MK-801-induced potentiation is a use-independent form of plasticity.
• But MK-801-induced potentiation shares the common expression mechanisms with LTP.
• MK-801-induced potentiation may lead to schizophrenia-like cognitive deficits.

Schizophrenia affects about 1% of the world population and is a major socio-economical problem in ours societies. Cognitive symptoms are particularly resistant to current treatments and are believed to be closely related to an altered function of prefrontal cortex (PFC). Particularly, abnormalities in the plasticity processes in the PFC are a candidate mechanism underlying cognitive symptoms, and the recent evidences in patients are in line with this hypothesis. Animal pharmacological models of cognitive symptoms, notably with non-competitive NMDA receptor antagonists such as MK-801, are commonly used to investigate the underlying cellular and molecular mechanisms of schizophrenia. However, it is still unknown whether in these animal models, impairments in plasticity of PFC neurons are present. In this article, we briefly summarize the current knowledge on the effect of non-competitive NMDA receptor antagonist MK-801 on medial PFC (mPFC) neuronal activity and then introduce a form of plasticity found after acute exposure to MK-801, which was accompanied by cognitive deficits. These observations suggest a potential correlation between cognitive deficits and the aberrant plasticity in the mPFC in the animal model of schizophrenia.