Blockade of behavioral sensitization by MK-801: fact or artifact? A review of preclinical data.
BACKGROUND
It is widely assumed that various forms of neural and behavioral plasticity, including sensitization, are strongly dependent on the activation of N-methyl-D-aspartate (NMDA)-receptors, but evidence also exists to suggest that not all forms of sensitization are unequivocally blocked by NMDA-receptor antagonism. Also, findings from studies examining the effects of NMDA-receptor blockade on forms of behavioral plasticity other than locomotor 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.


OBJECTIVE
Since the publication of two reviews addressing this issue in detail, this field of research has continued to be very active and controversial, and a number of further studies have been published in the meantime which are 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 contributions to the present discussion.


CONCLUSIONS
The studies reviewed herein have produced results both consistent with and in contradiction 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 other drugs in sensitization experiments is still in full swing. What seems crucial for future studies relating to this subject is a careful experimental design to reduce the number of potential interpretations of the findings.
Tzschentke
T M
TM
Grünenthal GmbH, Research and Development, Aachen, Germany. thomas.tzschentke@grunenthal.com
Schmidt
W J
WJ
D000818:Animals; D001519:Behavior / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006801:Humans
D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate