Locomotor reactivity to a novel environment and sensitivity to MK-801 in five strains of mice

Behav Pharmacol. 2008 Feb;19(1):71-5. doi: 10.1097/FBP.0b013e3282f3cf48.

Abstract

The ability of a noncompetitive antagonist of the N-methyl-D-aspartate receptor, MK-801, to stimulate locomotor activity (LMA) in mice was compared across CD-1, MF1, NIH Swiss (NIHS), C57BL6/J and BALB/C strains with the aim of identifying the most suitable strain for a putative model of schizophrenia. Animals were habituated to novel LMA cages for 1 h before receiving either saline or MK-801 (0.1, 0.32, or 0.5 mg/kg; i.p.) and activity recorded for 2 h. At the end of the test, blood and brain samples were taken and the total concentrations of MK-801 determined. Mice strains differed in habituation; C57BL6/J mice were the most active, whereas BALB/C mice were the least active and slowest to habituate. Robust strain-dependent differences in sensitivity to MK-801 were found, but not to saline. NIHS, C57BL6/J and BALB/C were more active in response to MK-801, exhibiting more rapid, robust and long-lasting increases in LMA than CD-1 or MF1 mice. Total concentrations of MK-801 in the brain did not differ across the strains. We found no correlation between the LMA stimulated by novelty and MK-801. NIHS, C57BL6/J and BALB/C appeared significantly more sensitive to MK-801 than CD-1 and MF1 and can be strains of choice in evaluating the effect of antipsychotic compounds in this model.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Brain / metabolism
  • Disease Models, Animal
  • Dizocilpine Maleate* / blood
  • Dizocilpine Maleate* / pharmacology
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects*
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Motor Activity / drug effects*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Schizophrenia / chemically induced
  • Species Specificity

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate