Locomotor reactivity to a novel environment and sensitivity to MK-801 in five strains of mice.
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.
Kalinichev
Mikhail
M
Biology Department, Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline plc, New Frontiers Science Park, Harlow, Essex, UK. mikhail.m.kalinichev@gsk.com
Bate
Simon T
ST
Coggon
Sara A
SA
Jones
Declan N C
DN
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000097:blood / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012559:Schizophrenia / Q000139:chemically induced; D013045:Species Specificity
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate