| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
In order to investigate the effects of aging on stress-induced increases in noradrenaline release in the rat brain, the two different aged male Wistar rats, 9 week and 12 month old, were subjected to the study. The rats were anesthetized with pentobarbital and implanted with a U-shaped dialysis probe into the anterior hypothalamus. All the experiments were carried out 24 hrs after the operation. The microdialysis probe was continuously perfused at a constant flow rate of 2 ml/min with an artificial cerebrospinal fluid. The microdialysis samples (40 μl/20 min) were collected for 60 min before stress exposure, then during stress exposure and for 80 min after release from stress. The two stress paradigms were employed, i.e., immobilization stress with a wire mesh and psychlogical stress where the rats were exposed to emotional responses such as struggling, vocalization, defecation and jumping shown by other electrically-shoked rats but received no electric shock by themselves. In acute ex
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periments, immobilization stress and psychological stress were continued for 120 min and 20 min, respectively. In the chronic experiments, the rats were exposed to immobilization stress for 120 min daily for 7 days. The noradrenaline contenst were determined by high liquid chromatography with electrochemical detection. Basal noradrenaline levels were not significantly different between young (9 week old) and aged (12 month old) rats. Although acute psychological stress and immobilization stress significantly increased noradrenaline release in the anterior hypothalamus in young rats and aged rats, the increase in young rats was significantly higher than that in aged rats. This finding suggested that the noradrenergic neuronal response to acute stress was attenuated in aged rats. Moreover, the degree of increases in noradrenaline release caused by immobilization stress is about two times greater than that induced by psychological stress, suggesting that the immobilization stress is a more intense stressor than is psychological stress. In young rats previously exposed to repeated immobilization stresses for 7 days, noradrenaline release elicited by 2 hrs of immobilizatioin stress or 20 min of psychological stress was significantly decreased as compared to that in naive rats exposed to stress. In contrast, in aged rats previously exposed to repeated immobilization stresses for 7 days, noradrenaline release elicited by psychological stress was further increased, however, noradrenaline release by immobilization stress was almost the same in naive rats exposed to stress. These results suggest that young rats can adapt to repeated stress, however, it is difficult for aged rats to adapt to repeated stressors.
Further we investigated immunohistochemically Fos-expression in the brain in young and aged rats exposed to stress. Fos-expression was observed in such brain regions as the paraventricular nucleus of the hypothalamus, locus coeruleus, the central nucleus of the amygdala, the medial prefrontal cortex and the paraventricular nucleus of the thalamus, suggesting that these brain regions were activated by immobilization stress, however, no difference between the young and aged rats was obatined. Further studise where such as repeated stresses or different stresses are employed should be needed. Less
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