TY - JOUR
T1 - Paradoxical effects of very low dose MK-801
AU - Tang, Yuanjia
AU - Zou, Hong
AU - Strong, Judith A.
AU - Cui, Yiwen
AU - Xie, Qinglian
AU - Zhao, Guoping
AU - Jin, Meilei
AU - Yu, Lei
N1 - Funding Information:
This work was supported in part by National Natural Science Foundation of China (30270219), and the National Institutes of Health (USA) grants (DA09444, DA13471, and DA12848). We thank Cheng Ding, Ning Guo, Junguo Hao, Neil Richtand, Jinhua Wu, and Ming Xu for helpful comments.
PY - 2006/5/10
Y1 - 2006/5/10
N2 - Systemic injection of the noncompetitive NMDA (N-methyl-d-aspartate) receptor antagonist MK-801 (dizocilpine maleate) is known to cause increased locomotion and various stereotypic behaviors in rodents. However, the MK-801 dose ranges commonly examined usually begin at tenth of mg/kg and going higher, with the implicit assumption of lower doses being ineffective. We report here that very low dose MK-801, well below the commonly studied doses, exert distinct effects on rodent behaviors. In C57BL/6 mice, very low dose MK-801 (0.02 mg/kg) has strikingly different effects than higher doses commonly reported in the literature. Locomotion, rearing, grooming, and other behaviors are strongly inhibited, replaced by periods of immobility. This is in contrast to the mobility-enhancing effect of MK-801 at commonly reported dose ranges. The effects of very low dose MK-801 are qualitatively similar to those observed with moderate doses (0.1-0.2 mg/kg) of the typical antipsychotic haloperidol. These results highlight the complexity of the dose-response relation for MK-801-induced behaviors.
AB - Systemic injection of the noncompetitive NMDA (N-methyl-d-aspartate) receptor antagonist MK-801 (dizocilpine maleate) is known to cause increased locomotion and various stereotypic behaviors in rodents. However, the MK-801 dose ranges commonly examined usually begin at tenth of mg/kg and going higher, with the implicit assumption of lower doses being ineffective. We report here that very low dose MK-801, well below the commonly studied doses, exert distinct effects on rodent behaviors. In C57BL/6 mice, very low dose MK-801 (0.02 mg/kg) has strikingly different effects than higher doses commonly reported in the literature. Locomotion, rearing, grooming, and other behaviors are strongly inhibited, replaced by periods of immobility. This is in contrast to the mobility-enhancing effect of MK-801 at commonly reported dose ranges. The effects of very low dose MK-801 are qualitatively similar to those observed with moderate doses (0.1-0.2 mg/kg) of the typical antipsychotic haloperidol. These results highlight the complexity of the dose-response relation for MK-801-induced behaviors.
KW - Catalepsy
KW - Dizocilpine maleate
KW - Haloperidol
KW - Immobility
KW - Locomotion
KW - NMDA receptor antagonist
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U2 - 10.1016/j.ejphar.2006.03.016
DO - 10.1016/j.ejphar.2006.03.016
M3 - Article
C2 - 16626696
AN - SCOPUS:33646467063
SN - 0014-2999
VL - 537
SP - 77
EP - 84
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -