MK-801 neurotoxicity in male mice: histologic effects and chronic impairment in spatial learning

MK-801 neurotoxicity in male mice: histologic effects and chronic impairment in spatial learning Several histological and behavioral experiments were conducted to investigate the neurotoxic effects of MK-801 in male mice. Moderate subcutaneous (s.c.) doses of MK-801 (0.5 and 1.0 mg/kg) induced the formation of intracytoplasmic vacuoles in pyramidal neurons in layers III and IV of the posterior cingulate/retrosplenial (PC/RS) cortex in 50% and 100% of the mice from the two respective treatment groups. Electron microscopic analysis of the vacuoles indicated that mitochondria and endoplasmic reticulum are the cellular organelles most prominently involved in this pathomorphological change. Treating mice with a high systemic dose of MK-801 (10 mg/kg s.c. or intraperitoneal (i.p.)) caused selective, irreversible degeneration of a small number of PC/RS cortical neurons. Compared to saline controls, the acquisition performance of mice treated i.p. with 10 mg/kg MK-801 was chronically impaired on a spatial learning task (modified hole board food search task) when tested at several posttreatment intervals (up to at least 5 months), although the groups did not differ on activity or sensorimotor tests conducted 2 weeks posttreatment. In summary, MK-801 caused histopathological changes in the mouse brain similar to those observed in the rat. Furthermore, high dose MK-801 treatment that killed a small number of mouse PC/RS cortical neurons resulted in a chronic acquisition impairment in spatial learning, an effect not previously demonstrated in any species. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

MK-801 neurotoxicity in male mice: histologic effects and chronic impairment in spatial learning

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Publisher
Elsevier
Copyright
Copyright © 1996 Elsevier Ltd
ISSN
0006-8993
DOI
10.1016/0006-8993(95)01230-3
Publisher site
See Article on Publisher Site

Abstract

Several histological and behavioral experiments were conducted to investigate the neurotoxic effects of MK-801 in male mice. Moderate subcutaneous (s.c.) doses of MK-801 (0.5 and 1.0 mg/kg) induced the formation of intracytoplasmic vacuoles in pyramidal neurons in layers III and IV of the posterior cingulate/retrosplenial (PC/RS) cortex in 50% and 100% of the mice from the two respective treatment groups. Electron microscopic analysis of the vacuoles indicated that mitochondria and endoplasmic reticulum are the cellular organelles most prominently involved in this pathomorphological change. Treating mice with a high systemic dose of MK-801 (10 mg/kg s.c. or intraperitoneal (i.p.)) caused selective, irreversible degeneration of a small number of PC/RS cortical neurons. Compared to saline controls, the acquisition performance of mice treated i.p. with 10 mg/kg MK-801 was chronically impaired on a spatial learning task (modified hole board food search task) when tested at several posttreatment intervals (up to at least 5 months), although the groups did not differ on activity or sensorimotor tests conducted 2 weeks posttreatment. In summary, MK-801 caused histopathological changes in the mouse brain similar to those observed in the rat. Furthermore, high dose MK-801 treatment that killed a small number of mouse PC/RS cortical neurons resulted in a chronic acquisition impairment in spatial learning, an effect not previously demonstrated in any species.

Journal

Brain ResearchElsevier

Published: Jan 29, 1996

References

  • Acute behavioral effects of MK-801 in the mouse
    Brosnan-Watters, G.; Wozniak, D.F.; Nardi, A.; Olney, J.W.
  • Quantitative analysis of factors influencing neuronal necrosis induced by MK-801 in the rat posterior cingulate/retrosplenial cortex
    Fix, A.S.; Wozniak, D.F.; Truex, L.L.; McEwen, M.; Miller, J.P.; Olney, J.W.
  • Posterior cingulate cortex in Alzheimer's disease
    Minoshima, S.; Foster, N.L.; Kuhl, D.E.
  • NMDA receptor hypofunction, excitotoxicity and Alzheimer's disease
    Olney, J.W.
  • Immediate and long-lasting effects of MK-801 on motor activity, spatial navigation in a swimming pool and EEG in the rat
    Whishaw, I.Q.; Auer, R.L.
  • Behavioral effects of MK-801 in the rat
    Wozniak, D.F.; Olney, J.W.; Kettinger, L.; Price, M.T.; Miller, J.P.

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