Parallel recovery of MK-801-induced spatial learning impairment and neuronal injury in male mice

G. Brosnan-Watters, D. F. Wozniak, A. Nardi, J. W. Olney

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


The relationship between spatial learning impairment and reversible neuronal injury in the posterior cingulate/retrosplenial (PC/RS) cortex induced by MK-801 in male mice was studied using a four-corner holeboard task. Mice were dosed with 1 mg/kg MK-801 and tested on acquisition of a new 'baited' hole at 5 or 12 h posttreatment. Acquisition in drugged mice was impaired at 5 h, but not at 12 h posttreatment. Their retention performances were unaffected 24 h after either the 5 or 12 h posttreatment acquisition sessions. MK-801 (1 mg/kg) was found to induce locomotor hyperactivity and some sensorimotor impairment at 5 h posttreatment, which could have contributed to the acquisition deficit. However, nonassociative effects of the drug were not prominent because this same dose did not impair holeboard performance at 5 h posttreatment when the task was well learned. Histologic experiments showed that many injured neurons (containing cytoplasmic vacuoles) were present in the PC/RS cortex at 5 h posttreatment but the reaction was essentially reversed at 12 h posttreatment. The results suggest that the acquisition impairment and neuronal injury induced by MK-801 evolve and recover in parallel according to a similar time schedule. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)111-122
Number of pages12
JournalPharmacology Biochemistry and Behavior
Issue number1
StatePublished - Jan 1999


  • Dizocilpine
  • MK-801
  • Mice
  • NMDA receptor antagonist
  • Neuronal injury
  • Sensorimotor
  • Spatial learning and memory


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