Bimodal effects of MK-801 on locomotion and stereotypy in C57BL/6 mice.
BACKGROUND
Systemic injection of the non-competitive NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 (dizocilpine maleate) causes both increased locomotion in rodents and various stereotypic behaviors that are proposed to model certain aspects of schizophrenic symptoms in humans.


OBJECTIVE
This study presents a comprehensive characterization of the bimodal effects of MK-801 on locomotion and stereotypy in the C57BL/6 mouse strain, a strain commonly used for genetically modified mice.


RESULTS
We found that it is important to analyze both locomotion and stereotypy in parallel, as MK-801-induced stereotypy results in abnormal movements that are recorded as locomotion by automated beam detection systems. Furthermore, it is important to analyze the bimodal effects of MK-801 over an extended time span, rather than the commonly used narrower time window, as at higher doses (e.g., above 0.3 mg/kg) the hyperlocomotion phase develops only after the stereotypic phase subsides. We also observed that the apparent dose-response curve is very sensitive to the particular time window chosen for analysis because MK-801 affects both the time course and maximum value of stimulated locomotion. We show that analyzing the absolute peak value of locomotion induced for each animal, rather than group-averaged time courses, provides a measure that is sensitive over a wider range of MK-801 doses. Interestingly, MK-801 even at a very low dose of 0.02 mg/kg suppressed rather than enhanced rearing behavior, differing in this regard from amphetamine.


CONCLUSIONS
The non-competitive NMDA receptor antagonist MK-801 induces a complex pattern of behavioral modification in mice with respect to both the time course and the dose-response relationship of behavioral changes. The results of this study provide a foundation and frame of reference for the growing interest in studying MK-801-induced behavior in mice.
Wu
Jinhua
J
Shanghai Research Center of Biotechnology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 500 Caobao Road, Shanghai, 200233, China.
Zou
Hong
H
Strong
Judith A
JA
Yu
Jun
J
Zhou
Xuedong
X
Xie
Qinglian
Q
Zhao
Guoping
G
Jin
Meilei
M
Yu
Lei
L
D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000502:physiology*; D011600:Psychopharmacology / Q000379:methods; D016194:Receptors, N-Methyl-D-Aspartate / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate