ENDURING EFFECTS OF CHRONIC CORTICOSTERONE TREATMENT ON SPATIAL-LEARNING, SYNAPTIC PLASTICITY, AND HIPPOCAMPAL NEUROPATHOLOGY IN YOUNG AND MID-AGED RATS

Prolonged treatment with stress levels of corticosterone has been repo rted to produce changes in the hippocampus, In the experiments reporte d here, we examined for functional and morphological consequences of t his treatment, First, young adult or mid-aged male Long-Evans rats wer e treated for either 1 or 3 months with corticosterone, at a dose suff icient to mimic the elevated hormone levels observed following exposur e to mild stress, Two weeks following the termination of treatment, th e animals were tested in the Morris water maze to assess spatial learn ing, No behavioral deficits were observed after 1 month of treatment, A 3 month treatment period also had no effect in young rats, but produ ced a learning impairment in the mid-aged rats, We then examined wheth er the effect of elevated corticosterone in mid-aged animals could be produced by a physiological stressor. Mid-aged rats were maintained fo r 6 months under conditions of low or high social stress, Six months o f exposure to high social stress produced significant spatial learning impairments in the Morris water maze, These effects were absent in hi gh social stress animals that had been previously adrenalectomized (wi th low-level corticosterone replacement), suggesting that elevated glu cocorticoid 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 th e diurnal peak (medium-B: 12-17 mu g/dl) or in response to stress (hig h-B: 25-32 mu g/dl). Only rats exposed to high levels of corticosteron e demonstrated impaired performance in the Morris water maze, Subseque nt electrophysiological studies revealed significantly reduced hippoca mpal synaptic plasticity in both medium-B and high-B animals. Cell cou nts indicated no significant changes in neuron density in the CA1 and CA3 pyramidal cell layer in either group of the corticosterone-treated rats. Taken together, the data demonstrate that long-term exposure to elevated corticosterone levels resulted in spatial learning deficits in mid-aged, but not young, rats, Further, these impairments do not ap pear to have been the consequence of hippocampal neuron loss.