Paradoxical effects of very low dose MK-801

European Journal of Pharmacology
Yuanjia TangLei Yu

Abstract

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.

References

Jan 1, 1990·Journal of Neural Transmission. General Section·P I TiedtkeW J Schmidt
Jul 1, 1997·Neuroscience and Biobehavioral Reviews·W J Schmidt, B D Kretschmer
Apr 12, 2003·Neuropharmacology·Kathryn M AbelMark A Geyer
Jul 5, 2003·Neuropharmacology·Ludovic LerichePierre Sokoloff
May 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Mark E JacksonBita Moghaddam
Aug 4, 2004·Psychopharmacology·Jinhua WuLei Yu

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Citations

Feb 12, 2011·Behavioural Brain Research·F Josef van der StaayArjan Blokland
Jan 29, 2008·Journal of Neurochemistry·Lola GaleoteFernando Berrendero
Aug 11, 2015·Schizophrenia Research·Dragos IntaPeter Gass
Jan 7, 2020·Experimental Neurobiology·Darine Froy N MabungaSe Jin Jeon

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