Paradoxical effects of very low dose MK-801

Yuanjia Tang, Hong Zou, Judith A. Strong, Yiwen Cui, Qinglian Xie, Guoping Zhao, Meilei Jin, Lei Yu

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)77-84
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number1-3
StatePublished - May 10 2006

All Science Journal Classification (ASJC) codes

  • Pharmacology


  • Catalepsy
  • Dizocilpine maleate
  • Haloperidol
  • Immobility
  • Locomotion
  • NMDA receptor antagonist


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