Blockade of behavioral sensitization by MK-801: fact or artifact? A reviewof preclinical data

Rationale: It is widely assumed that various forms of neural and behavioral plasticity, including sensitization, are strongly dependent on the activat ion of N-methyl-D-aspartate (NMDA)-receptors, but evidence also exists to s uggest that not all forms of sensitization are unequivocally blocked by NMD A-receptor antagonism. Also, findings from studies examining the effects of NMDA-receptor blockade on forms of behavioral plasticity other than locomo tor sensitization (various forms of tolerance, sensitization of catalepsy, and learning and conditioning) reinforce the view that forms of behavioral plasticity exist that are not blocked by NMDA-receptor antagonists. Objecti ves: Since the publication of two reviews addressing this issue in detail, this field of research has continued to be very active and controversial, a nd a number of further studies have been published in the meantime which ar e relevant to the topic. The aim of this review is to provide a summary of this literature and to consider new approaches that might make important co ntributions to the present discussion. Results and conclusions: The studies reviewed herein have produced results both consistent with and in contradi ction to the view that MK-801 and related drugs block behavioral plasticity , and the debate about how exactly MK-801 and related drugs interact with o ther drugs in sensitization experiments is still in full swing. What seems crucial for future studies relating to this subject is a careful experiment al design to reduce the number of potential interpretations of the findings .