Parallel recovery of MK-801-induced spatial learning impairment and neuronal injury in male mice.
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.
Brosnan-Watters
G
G
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
Wozniak
D F
DF
Nardi
A
A
Olney
J W
JW
D000704:Analysis of Variance; D000818:Animals; D016291:Dizocilpine Maleate / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D007858:Learning / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D011597:Psychomotor Performance / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*