A facilitative role for corticosterone in the acquisition of a spatial task under moderate stress

Abstract

Emotionally charged experiences alter memory storage via the activation of hormonal systems. Previously, we have shown that compared with rats trained for a massed spatial learning task in the water maze in warm water (25 degrees C), animals that were trained in cold water (19 degrees C) performed better and showed higher levels of the stress hormone corticosterone. Here, we examined whether manipulating the levels of corticosterone can determine the strength of spatial information acquisition and retention. Rats were injected with metyrapone (25, 50, and 75 mg/kg, i.p.) or with corticosterone (10 and 25 mg/kg, i.p.) and trained in a massed spatial task in either cold (19 degrees C) or warm (25 degrees C) water. We found that whereas animals injected with vehicle performed well in the spatial task in cold water (moderate stress), rats injected with the intermediate metyrapone dose showed impairment in performance. Moreover, whereas animals injected with vehicle on average did not perform well in warm water (mild stress), rats injected with the lower corticosterone dose showed improvement in performance in warm water. These two mirror experiments of corticosterone blockade and enhancement strongly suggest that corticosterone is instrumental in the acquisition and retention of the spatial learning task.

Figure 1

Myterapone decreases and corticosterone increases circulating corticosterone levels. A significant difference in corticosterone levels (data represent the means ± SEM expressed as nanogram/milliliter) was found between the vehicle cold water and the 50 mg/kg metyrapone cold water groups (50Met Cold Water; ^*, P < 0.001), and a significant difference between the vehicle warm water and the 10 mg/kg corticosterone warm water groups (10CORT Warm Water, ^*, P < 0.05). Thus, 50 mg/kg metyrapone reduced and 10 mg/kg CORT increased circulating corticosterone levels. Additionally, there was a significant difference between the vehicle warm water and vehicle cold water group (^*, P < 0.01), which further supports the notion that training in cold water is more stressful (i.e., results in higher corticosterone levels) than training in warm water.

Figure 2

Massed training at different water temperatures differentially affects the performance of rats in the spatial task. (A) All animals trained at 19°C (Cold Water) have acquired the task. Animals trained at 25°C were divided into two groups, animals that reached the platform four consecutive times in 20 sec or less [Warm Water (+)] and animals that showed higher latencies in reaching the platform [Warm Water (-)]. A significant difference in performance (measured as escape latency) was found between the Warm Water (-) group and both the Cold Water (P < 0.001) and the Warm Water (+) (P < 0.001) groups, with no significant difference between the Cold Water and the Warm Water (+) groups. (B) A quadrant analysis test was conducted 1 h following the last behavioral trial. Rats in the Cold Water group showed a significant bias to swim the longest distance within the quadrant in which the platform had been located previously (Q2; ^* significant difference from chance level (25%): P < 0.0001). In contrast, the Warm Water (+) and the Warm Water (-) groups showed no such bias. This may suggest a primary difference in the quality of the spatial memory between the animals trained in cold water and the good performers of the warm water group, which although they performed well in training (A), failed to perform well in the test (B).

Figure 3

Metyrapone dose dependently affects the performance of animals trained in a massed schedule in cold water. (A) A significant difference in performance (measured as escape latency) was found between the Cold Water group and both the 50Met Cold Water (P < 0.05) and the 75Met Cold Water (P < 0.05) groups, with no significant difference between the Cold Water and the 25Met Cold Water group. In addition, the 25Met Cold Water group was significantly different from both the 50Met Cold Water (P < 0.05) and the 75Met Cold Water (P < 0.05) groups, with no significant difference between the 50Met Cold Water and the 75Met Cold Water groups. This suggests a concentration-dependent effect of metyrapone on the performance in the massed spatial task, i.e., the higher the metyrapone dose, the worse the performance. (B) In the quadrant test, the Cold Water group showed a significant bias to swim the longest distance within the quadrant in which the platform had been located previously (Q2; ^*, P < 0.0001). However, all the other groups showed no such bias.

Figure 4

Corticosterone dose dependently affects the performance of animals trained in warm water. (A) A significant difference in performance (measured as escape latency) was found between the Warm Water (+) group and both the Warm Water (-) (P < 0.001), and the 25CORT Warm Water (P < 0.01) groups, but not between the Warm Water (+) group and the 10CORT Warm Water group. In addition, there was a significant difference between the 10CORT Warm Water group and both the Warm Water (-) (P < 0.001) and the 25CORT Warm Water (P < 0.001) groups, but not between the Warm Water (-) group and the 25CORT Warm Water group. This suggests a concentration-dependent facilitative effect of corticosterone on the performance in the spatial learning task. (B) In the quadrant test, the 10CORT Warm Water group showed a significant bias to swim the longest distance within the quadrant in which the platform had been located previously (Q2; ^*, P < 0.05). In contrast, the 25CORT Warm Water group showed no such bias.

Figure 5

Animals treated with both metyrapone and corticosterone show good performance in cold water. (A) No significant difference in performance (measured as escape latency) was found between the Vehicle group and the Met and CORT group. Thus the effects of metyrapone (Fig. 3) are mainly due to its effect on the glucocorticoid system. (B) In the quadrant test, both the vehicle and the Met and CORT groups showed a significant bias to swim the longest distance within the quadrant in which the platform had been located previously (Q2; Vehicle:^*, P < 0.01, Met and CORT:^*, P < 0.05).