G. Brosnan-watters et al., Differential effects of MK-801 on cerebrocortical neuronal injury in C57BL/6J, NSA, and ICR mice, PROG NEUR-P, 24(6), 2000, pp. 925-938
Citations number
25
Categorie Soggetti
Neurosciences & Behavoir
Journal title
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
1. Antagonists of the N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor,
including [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imin
e maleate], dizocilpine maleate (MK-801), injure pyramidal neurons in the p
osterior cingulate/retrosplenial (PC/RS) cortex when administered systemica
lly to adult rats and mice.
2. These results have, to our knowledge, only been reported previously in H
arlan Sprague Dawley albino rats and International Cancer Research (ICR) mi
ce, an outbred albino strain.
3. Male Non-Swiss Albino (NSA) mice, an albino outbred strain, and male C57
BL/6J (B6) mice, a pigmented inbred strain, were injected systemically with
1 mg/kg of MK-801 in the first experiment. This dose of MK-801 reliably pr
oduces cytoplasmic vacuoles in neurons in layers III and IV of the PC/RS co
rtex in 100% of ICR mice treated.
4. There was a significant difference in the number of vacuolated neurons i
n B6 and NSA mice, as assessed by ANOVA. The NSA were not significantly dif
ferent than previously examined ICR mice, but the B6 had fewer vacuolated n
eurons than either of the two outbred strains.
5. In the second experiment, male NSA, ICR, and B6 mice were injected syste
mically with a high dose, 10 mg/kg, of MK-801. This dose has been demonstra
ted to result in necrosis in the same population of neurons injured by lowe
r doses of MK-801.
6. An ANOVA indicated that there was a significant difference among the thr
ee strains of mice, and a Fisher's protected t revealed that the B6 mice we
re significantly different from both the NSA and ICR, but that, with our te
st, those two strains were indistinguishable.
7. Male ICR, NSA, and B6 mice were tested in the holeboard food search task
5 hours after 1 mg/kg of MK-801. There were significant differences betwee
n the strains in performance both pre and posttreatment. The effect of the
drug was not statistically significant.
8.These results suggest that there may be a genetically mediated difference
in the reaction to NMDA receptor antagonists, a finding which may be impor
tant given the NMDA receptor hypofunction hypothesis for the etiology of sc
hizophrenic symptoms.