|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1999 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1998 : ¥2,000,000 (Direct Cost : ¥2,000,000)
At first, we investigated whether nitric oxide synthase (NOS) gene was induced by immobilization stress (IMS) in rat hypothalamus, hippocampus, cerebral cortex, and cerebellum, using reverse transcription-polymerase chain reaction. Animals were treated in accordance with the National Institutes of Health guide for the care and use of Laboratory animals. Immobilization stress induced the expression of iNOS mRNA in every brain region examined with a peak around 30 or 60 min. This result suggests that, since iNOS is tanscriptionally-regulated enzyme, it is induced by stress exposure in the brain.
The objection of the second experiment was that we investigated whether nitric oxide (NO) levels changed after the initiation of IMS in the hypothalamus of free-moving rats, Rats were anesthetized and inplanted a guide canule in the hypothalamus. After 1 week, a microdialysis probe was inserted into the hypothalamus and was perfused with Hanks's solution. The dialysate were injected in an automate
d NO detector-hyperformance-liquid-chromatography system (ENO-10, Eicom, Kyoto, Japan) directly. Four or more hours later, assays of NOィイD3-(/)2ィエD3 and NOィイD3-(/)3ィエD3 levels were started, and then the basal levels were measured for two or more hours. Between 40 and 120 min after starting of iMS, NOィイD3-(/)2ィエD3 and NOィイD3-(/)3ィエD3 levels increased significantly.
Finally, we investigated plasma NOィイD3-(/)2ィエD3 and NOィイD3-(/)3ィエD3 levels in untreated 17 patients with depressive episodes, untreated seven patients with anxiety disorders, and 12 healthy controls. Written informed consent was obtained from each individual.
No significant difference was found in plasma nitrite levels among the groups. Plasma NOィイD3-(/)3ィエD3 levels in depressed patients were significantly higher than those in controls or patients with anxiety disorders (Scheffe's F test, P<0.05, figure). Moreover, in patients with depressive episodes, nitrate levels significantly decreased, approximately to control levels, after recovery (Wilcoxon signed-ranks test, P<0.01, figure).
Unclear remains the source of the surplus production of nitric oxide in patients with depressive episodes. However, measurement of plasma nitrate levels might be useful in the differential diagnosis of affective disorders versus anxiety disorders. Less