Existence of Triggering Mechanism in the Stress Response(the 39th Annual Congress of the Japanese Society of Psychosomatic Medicine)

Abstract

We have reported that a variety of stressful stimuli cause marked increases in noradrenaline (NA) release in the extended brain regions in the rats by measuring levels of both regional NA and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-S04) and by utilizing intracerebral microdialysis technique. Usually, the period of stress exposure employed in these studies was more than 30 min. However, a very short duration of stress such as immobilization stress only for 1 min could increase NA release in such brain regions as the hypothalamus, Iocus coeruleus (LC) region, hippocampus, cerebral cortex and midbrain 20 or 40 min after cessation of stress to the extent of those caused by continuous stress for 45 min. Although diazepam, a typical anxiolytic of benzodiazepines, significantly attenuated increases in NA release caused by stress in such brain regions as the hypothalamus, amygdala and LC region, etc., these effects of diazepam were observed only when the drug was administered immediately before, but neither 10 min before nor 10 min after stress exposure. Met-Enkephalin, an opioid peptide, injected i.c.v., also attenuated stress-induced increases in NA release in the brain regions, however, these attenuating effects appeared when the peptide was administered only immediately before, but neither 5 min nor 10 min after stress exposure. Met-Enkephalin, injected only immediately before stress exposure, significantly attenuated emotional responses such as defecation and weight loss shown by stressed rats. These findings suggest that there might exist the triggering mechanism, which once the animal was exposed to stress, even if such a short period as 1 min, begins to cause serial stress responses, which resulted in increases in NA release in the extended brain regions induced by 1 min immobilization stress followed by 20 or 40 min rest. The finding that alpha-helical CRF, an antagonist of corticotropin releasing factor (CRF) , administered immediately before stress exposure, significantly attenuated stress-induced increases in brain NA release, suggests that CRF could be involved, in part, in this triggering system. The recent findings on psychoneuroimmunomodulation suggest the involvement of immune system in this alarm mechanism.