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Memory retrieval impairment induced by hippocampal CA3 lesions is blocked by adrenocortical suppression
B Roozendaal1, R G Phillips, A E Power
1Center for the Neurobiology of Learning and Memory, and Department of Neurobiology and Behavior, University of California, Irvine, California 92697-3800, USA. broozend@uci.edu
Insights
Hippocampal damage impairs spatial memory retrieval in rats. Inhibiting corticosterone, a stress hormone, with metyrapone reversed these memory deficits, suggesting a critical role for the HPA axis.
Area of Science:
- Neuroscience
- Memory Research
- Endocrinology
Background:
- Hippocampal lesions, particularly in the CA3 subfield, are known to impair spatial memory retrieval in rats.
- Hippocampal damage also leads to disinhibition of the hypothalamic-pituitary-adrenocortical (HPA) axis, increasing stress hormone levels.
Purpose of the Study:
- To investigate the role of elevated adrenocortical activity in mediating memory retrieval deficits following hippocampal damage.
- To determine if inhibiting corticosterone synthesis can ameliorate lesion-induced memory impairments.
Main Methods:
- Rats with partial hippocampal CA3 lesions were used.
- Metyrapone, a synthesis inhibitor of corticosterone, was administered before water-maze retention testing.
- Plasma corticosterone levels and memory retrieval performance were assessed.
Main Results:
- CA3 lesions resulted in impaired spatial memory retrieval and elevated plasma corticosterone levels.
- Administration of metyrapone attenuated the lesion-induced increase in corticosterone.
- Blocking the rise in corticosterone levels with metyrapone prevented the memory retrieval deficits.
Conclusions:
- Elevated adrenocortical activity, specifically increased corticosterone, is critical for mediating memory retrieval deficits caused by hippocampal damage.
- The HPA axis plays a significant role in the cognitive impairments associated with hippocampal injury.
Abstract:
There is evidence that in rats, partial hippocampal lesions or selective ablation of the CA3 subfield can disrupt retrieval of spatial memory and that hippocampal damage disinhibits hypothalamic-pituitary-adrenocortical (HPA)-axis activity, thereby elevating plasma levels of adrenocorticotropin and corticosterone. Here we report evidence that attenuation of CA3 lesion-induced increases in circulating corticosterone levels with the synthesis inhibitor metyrapone, administered shortly before water-maze retention testing, blocks the impairing effects of the lesion on memory retrieval. These findings suggest that elevated adrenocortical activity is critical in mediating memory retrieval deficits induced by hippocampal damage.