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.
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.
Authors: Vivian W Chow; Alena V Savonenko; Tatiana Melnikova; Hyunsu Kim; Donald L Price; Tong Li; Philip C Wong Journal: Sci Transl Med Date: 2010-01-06 Impact factor: 17.956
Authors: Christopher T Wild; Joanna M Miszkiel; Eric A Wold; Claudia A Soto; Chunyong Ding; Rachel M Hartley; Mark A White; Noelle C Anastasio; Kathryn A Cunningham; Jia Zhou Journal: J Med Chem Date: 2018-04-13 Impact factor: 7.446
Authors: Kathryn A Cunningham; Robert G Fox; Noelle C Anastasio; Marcy J Bubar; Sonja J Stutz; F Gerard Moeller; Scott R Gilbertson; Sharon Rosenzweig-Lipson Journal: Neuropharmacology Date: 2011-05-11 Impact factor: 5.250
Authors: Stephen C Fowler; Benjamin R Miller; Thomas W Gaither; Michael A Johnson; George V Rebec Journal: Behav Brain Res Date: 2009-03-28 Impact factor: 3.332