Does the noncompetitive NMDA receptor antagonist dizocilpine (MK801) really block behavioural sensitization associated with repeated drug administration?

The term 'behavioural sensitization' refers to the progressively augmented behavioural response that is produced by many drugs of abuse upon their repeated administration. From most of the available data, it has been concluded that co-administration of an N-methyl-D-aspartate (NMDA) receptor antagonist [such as dizocilpine (MK801)] together with the sensitizing drug can block the development of behavioural sensitization. However, the picture might not be that simple. Recent experimental evidence suggests that instead of blocking sensitization, co-administration of dizocilpine enhances the effect of the sensitizing drug or has more complex effects on the development of sensitization. In this article, Thomas Tzschentke and Warner Schmidt present these two different views and emphasize that the conclusions that can be drawn from sensitization experiments about the effects of dizocilpine and related drugs on behavioural plasticity crucially depend on how, when and under what conditions a test for sensitization is conducted.