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Bimodal effects of MK-801 on locomotion and stereotypy in C57BL/6 mice

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Abstract

Rationale

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.

Objectives

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.

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Acknowledgments

This work was supported in part by National Natural Science Foundation of China (30270219) and National Institutes of Health (USA) grants (DA09444, DA13471, and DA12848). We thank Johanna Meij, Ning Guo, Lingyan Wang, Cheng Ding, and Yuanjia Tang for helpful comments. The experiments reported herein comply with the current laws of the People’s Republic of China and the United States of America.

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Authors and Affiliations

  1. Shanghai Research Center of Biotechnology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 500 Caobao Road, Shanghai, 200233, China

    Jinhua Wu, Hong Zou, Jun Yu, Xuedong Zhou, Qinglian Xie, Guoping Zhao & Meilei Jin

  2. Department of Cell Biology, Neurobiology & Anatomy, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521, USA

    Judith A. Strong & Lei Yu

Authors
  1. Jinhua Wu
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  2. Hong Zou
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  3. Judith A. Strong
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  4. Jun Yu
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  5. Xuedong Zhou
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  6. Qinglian Xie
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  7. Guoping Zhao
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  8. Meilei Jin
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  9. Lei Yu
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Corresponding author

Correspondence to Lei Yu.

Additional information

The first three authors contributed equally to this work.

Co-corresponding authors: Guoping Zhao, Meilei Jin, Lei Yu

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Wu, J., Zou, H., Strong, J.A. et al. Bimodal effects of MK-801 on locomotion and stereotypy in C57BL/6 mice. Psychopharmacology 177, 256–263 (2005). https://doi.org/10.1007/s00213-004-1944-1

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  • DOI: https://doi.org/10.1007/s00213-004-1944-1

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