Consequences of early life MK-801 administration: Long-term behavioural effects and relevance to schizophrenia research

Animal models contribute significantly to advancing the understanding of schizophrenia neurobiology, in addition to being an important tool for the screening of antipsychotic potential of new compounds. However, the entire spectrum or all the symptoms manifested in schizophrenia cannot be straightforwardly reproduced in animals due to the complexity of the disorder, difference in mental capacities and behaviours, and the ability to quantify or measure the changes. Blockade of the NMDA receptor by the use of MK-801, a non-competitive NMDA receptor antagonist, during the early postnatal period has been proposed to be an experimental model which induces behavioural changes that mimic several aspects of the disorder. The long term behavioural profile arising from this early life manipulation is reviewed herein, with a specific focus on behaviours relevant to a schizophrenia-like condition. Some of the reported neurochemical changes are also compiled. Although this method may be suitable to model some aspects of schizophrenia in rodents, there are unmet areas which need to be addressed, notably the characterisation of its predictive value.

► Long term psychoses-relevant effects of neonatal MK-801 treatment are reviewed.
► Construct validity for MK-801-induced psychotic-like effects is satisfactory.
► Face and predictive validity for MK-801-induced psychotic-like effects is outlined.