Studies have shown that peripheral levels of corticosterone correlate with the magnitudes of two well-described physiological models of memory, long-term potentiation (LTP) and primed burst (PB) potentiation. In the present experiments, the authors investigated the effects of experimenter-controlled manipulations of the levels of corticosterone on the magnitude of hippocampal PB potentiation in urethane-anesthetized rats. Primed burst potentiation is a long-lasting (at least 30 minutes) increase in the amplitude of the CA1 population spike and EPSP slope in response to physiologically patterned stimulation of the hippocampal commissure. The levels of serum corticosterone were controlled by implanting corticosterone pellets in adrenalectomized rats (ADX/PELLET). In the first experiment, a significant negative linear correlation between elevated (stress) levels of serum corticosterone (greater than 20 micrograms/dL) and the magnitude of PB potentiation in ADX/PELLET subjects (r = 0.60, P < .05) was found. In the second experiment, the shape of the corticosterone-PB potentiation function was different at low and intermediate levels of corticosterone than it was at high levels of corticosterone: There was a positive correlation at low levels (0-10 micrograms/dL), a peak response at intermediate levels (11-20 micrograms/dL), and a negative correlation at high levels (21-93 micrograms/dL) of corticosterone. Thus, the overall relationship between corticosterone and PB potentiation is an inverted-U function. These findings provide strong support for the hypothesis that corticosterone exerts a concentration-dependent biphasic influence on the expression of hippocampal plasticity.
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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