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Journal of Neuroscience, Vol 15, 61-69, Copyright © 1995 by Society for Neuroscience
Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats
SR Bodnoff, AG Humphreys, JC Lehman, DM Diamond, GM Rose and MJ Meaney
Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal, Canada.
Prolonged treatment with stress levels of corticosterone has been reported
to produce changes in the hippocampus. In the experiments reported here, we
examined for functional and morphological consequences of this treatment.
First, young adult or mid-aged male Long-Evans rats were treated for either
1 or 3 months with corticosterone, at a dose sufficient to mimic the
elevated hormone levels observed following exposure to mild stress. Two
weeks following the termination of treatment, the animals were tested in
the Morris water maze to assess spatial learning. No behavioral deficits
were observed after 1 month of treatment. A 3 month treatment period also
had no effect in young rats, but produced a learning impairment in the
mid-aged rats. We then examined whether the effect of elevated
corticosterone in mid-aged animals could be produced by a physiological
stressor. Mid-aged rats were maintained for 6 months under conditions of
low or high social stress. Six months of exposure to high social stress
produced significant spatial learning impairments in the Morris water maze.
These effects were absent in high social stress animals that had been
previously adrenalectomized (with low-level corticosterone replacement),
suggesting that elevated glucocorticoid levels mediate the effects of
stress on spatial memory in older animals. In a final experiment, mid-aged
rats were treated with corticosterone at levels that mimicked those
naturally occurring at the diurnal peak (medium-B: 12-17 micrograms/dl) or
in response to stress (high-B: 25-32 micrograms/dl). Only rats exposed to
high levels of corticosterone demonstrated impaired performance in the
Morris water maze.(ABSTRACT TRUNCATED AT 250 WORDS)
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